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Xu Y, Peng J, Zhou X, Huang Y, Zhong G, Xia Z. Association of 25-hydroxyvitamin D with Parkinson's disease based on the results from the NHANES 2007 to 2018 and Mendelian randomization analysis. Sci Rep 2025; 15:5514. [PMID: 39953081 PMCID: PMC11828982 DOI: 10.1038/s41598-025-87120-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 01/16/2025] [Indexed: 02/17/2025] Open
Abstract
An abundance of observational researches had suggested that vitamin D insufficient was related to Parkinson's disease (PD) risk. However, their relationships were debatable and the causality remains uncertain. We intended to evaluate the association between 25-hydroxyvitamin D [25(OH)D] and Parkinson's disease (PD) risk using NHANES data (2007-2018) and Mendelian randomization (MR) analyses with the genome-wide association study (GWAS) summary data. Demographic characteristics and multivariable-adjusted logistic regression were conducted to assess the relationship between the serum 25(OH)D levels and risk of PD prevalence by utilizing NHANES database. Besides, a two-sample MR analysis was applied to evaluate the causal association between serum 25(OH)D levels and PD risk. The main analysis was conducted by citing the inverse-variance-weighted (IVW) approach, while additional MR approaches and multiple sensitivity analysis were cited to evaluate the robustness and pleiotropy for the discoveries. In total, 30,796 adults from NHANES 2007-2018 were selected for the present research. As a result, 1.1% participants with PD (mean age: 61.9 ± 15.5 years), while 68.5% reported vitamin D insufficient. Compared with participants without PD, those with PD had a greater level of 25(OH)D (P < 0.01). However, after adjusted for demographic characteristics and comorbid factors, this association was not observed. Furthermore, no potential causal relationships between the serum level of 25(OH)D and PD risk were found via MR analysis (IVW-MR: OR = 1.082; 95% CI, 0.902 to 1.297; P = 0.395). After eliminating variants with horizontal pleiotropy risk, pleiotropy-robust MR analysis presented similar results. In conclusion, this research suggested that serum 25(OH)D levels was not correlated with PD risk. Additionally, the MR analyses revealed no significant causal association between serum 25(OH)D levels and PD risk at the genetic level. Awareness of these findings may improve personalized prevention and treatment of PD.
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Affiliation(s)
- Yan Xu
- Department of Clinical Laboratory, Hunan Aerospace Hospital, Hunan Normal University, Changsha, Hunan, China
| | - Jie Peng
- Department of Blood Transfusion, Hunan Aerospace Hospital, Hunan Normal University, Changsha, Hunan, China
| | - Xiguo Zhou
- Hunan Center for Clinical Laboratory, Changsha, Hunan, China
| | - Yuexin Huang
- Department of Urology, Hunan Aerospace Hospital, Hunan Normal University, Changsha, Hunan, China
| | - Guanzhen Zhong
- Department of Anesthesiology, Hunan Aerospace Hospital, Hunan Normal University, Changsha, Hunan, China.
| | - Zhiwei Xia
- Medical Center for Neurological Disease, Hunan Aerospace Hospital, Hunan Normal University, Changsha, Hunan, China.
- Department of Neurology, Hunan Aerospace Hospital, Hunan Normal University, Changsha, Hunan, China.
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Hosseini SM, Panahi-Azar A, Sheybani-Arani M, Morovatshoar R, Mirzadeh M, Salimi Asl A, Naghdipour Mirsadeghi M, Khajavi-Mayvan F. Vitamins, minerals and their maternal levels' role in brain development: An updated literature-review. Clin Nutr ESPEN 2024; 63:31-45. [PMID: 38907995 DOI: 10.1016/j.clnesp.2024.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 03/26/2024] [Accepted: 05/16/2024] [Indexed: 06/24/2024]
Abstract
One's neurobehavioural and mental health are built during the exact and complex process of brain development. It is thought that fetal development is where neuropsychiatric disorders first emerged. Behavioural patterns can change as a result of neuropsychiatric illnesses. The incidence is rising quickly; nevertheless, providing exceptional care remains a significant challenge for families and healthcare systems. It has been demonstrated that one of the main factors causing the transmission of these diseases is maternal exposure. Through physiologic pathways, maternal health and intrauterine exposures can affect brain development. Our attention has been focused on epigenetic factors, particularly in the gestational environment, which may be responsible for human neurodegenerative diseases since our main mental development occurs during the nine months of intrauterine life. After thoroughly searching numerous databases, this study examined the effect of fat-soluble vitamins, water-soluble vitamins, and minerals and their maternal-level effect on brain development.
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Affiliation(s)
| | - Ava Panahi-Azar
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
| | | | - Reza Morovatshoar
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
| | - Mahdieh Mirzadeh
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
| | - Ali Salimi Asl
- Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
| | - Misa Naghdipour Mirsadeghi
- Department of Gynecology, School of Medicine, Reproductive Health Research Center, Alzahra Hospital, Guilan University of Medical Sciences, Rasht, Iran.
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Skv M, Abraham SM, Eshwari O, Golla K, Jhelum P, Maity S, Komal P. Tremendous Fidelity of Vitamin D3 in Age-related Neurological Disorders. Mol Neurobiol 2024; 61:7211-7238. [PMID: 38372958 DOI: 10.1007/s12035-024-03989-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Accepted: 01/23/2024] [Indexed: 02/20/2024]
Abstract
Vitamin D3 (VD) is a secosteroid hormone and shows a pleiotropic effect in brain-related disorders where it regulates redox imbalance, inflammation, apoptosis, energy production, and growth factor synthesis. Vitamin D3's active metabolic form, 1,25-dihydroxy Vitamin D3 (1,25(OH)2D3 or calcitriol), is a known regulator of several genes involved in neuroplasticity, neuroprotection, neurotropism, and neuroinflammation. Multiple studies suggest that VD deficiency can be proposed as a risk factor for the development of several age-related neurological disorders. The evidence for low serum levels of 25-hydroxy Vitamin D3 (25(OH)D3 or calcidiol), the major circulating form of VD, is associated with an increased risk of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), dementia, and cognitive impairment. Despite decades of evidence on low VD association with neurological disorders, the precise molecular mechanism behind its beneficial effect remains controversial. Here, we will be delving into the neurobiological importance of VD and discuss its benefits in different neuropsychiatric disorders. The focus will be on AD, PD, and HD as they share some common clinical, pathological, and epidemiological features. The central focus will be on the different attributes of VD in the aspect of its anti-oxidative, anti-inflammatory, anti-apoptotic, anti-cholinesterase activity, and psychotropic effect in different neurodegenerative diseases.
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Affiliation(s)
- Manjari Skv
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Sharon Mariam Abraham
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Omalur Eshwari
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Kishore Golla
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Priya Jhelum
- Centre for Research in Neuroscience and Brain Program, The Research Instituteof the, McGill University Health Centre , Montreal, QC, Canada
| | - Shuvadeep Maity
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Pragya Komal
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India.
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Zhou QL, Ye D, Ren PC, Pang WB, Lin XM, Cao RH, Ye XS, Xiang W, Xiao L. A multi-omics analysis reveals vitamin D supplementation since childhood modulates molecules for signal transductions in the mouse striatum. Biomed Pharmacother 2024; 178:117145. [PMID: 39038374 DOI: 10.1016/j.biopha.2024.117145] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 07/02/2024] [Accepted: 07/11/2024] [Indexed: 07/24/2024] Open
Abstract
Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management.
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Affiliation(s)
- Q L Zhou
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Basic Medicine and Life Science, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - D Ye
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - P C Ren
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Basic Medicine and Life Science, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - W B Pang
- School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - X M Lin
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Basic Medicine and Life Science, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - R H Cao
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - X S Ye
- School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China
| | - W Xiang
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China.
| | - L Xiao
- Hainan Women and Children's Medical Center, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China; School of Pediatrics, Hainan Medical University, Hainan Academy of Medical Sciences, Haikou, China.
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Li HH, Wang XF, Wang B, Jia FY. Vitamin D3 improves iminodipropionitrile-induced tic-like behavior in rats through regulation of GDNF/c-Ret signaling activity. Eur Child Adolesc Psychiatry 2024; 33:3189-3201. [PMID: 38396228 DOI: 10.1007/s00787-024-02376-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 01/08/2024] [Indexed: 02/25/2024]
Abstract
Children with chronic tic disorders (CTD), including Tourette syndrome (TS), have significantly reduced serum 25-hydroxyvitamin D [25(OH)D]. While vitamin D3 supplementation (VDS) may reduce tic symptoms in these children, its mechanism is unclear. The study aim was to investigate the effects and mechanisms of vitamin D deficiency (VDD) and VDS on TS model behavior. Forty 5-week-old male Sprague-Dawley rats were randomly divided into (n = 10 each): control, TS model, TS model with VDD (TS + VDD), or TS model with VDS (TS + VDS; two intramuscular injections of 20,000 IU/200 g) groups. The VDD model was diet-induced (0 IU vitamin D/kg); the TS model was iminodipropionitrile (IDPN)-induced. All groups were tested for behavior, serum and striatal 25(OH)D and dopamine (DA), mRNA expressions of vitamin D receptor (VDR), glial cell line-derived neurotrophic factor (GDNF), protooncogene tyrosine-protein kinase receptor Ret (c-Ret), and DA D1 (DRD1) and D2 (DRD2) receptor genes in the striatum. TS + VDD had higher behavior activity scores throughout, and higher total behavior score at day 21 compared with TS model. In contrast, day 21 TS + VDS stereotyped behavior scores and total scores were lower than TS model. The serum 25(OH)D in TS + VDD was < 20 ng/mL, and lower than control. Striatal DA of TS was lower than control. Compared with TS model, striatal DA of TS + VDD was lower, while in TS + VDS it was higher than TS model. Furthermore, mRNA expression of VDR, GDNF, and c-Ret genes decreased in TS model, and GDNF expression decreased more in TS + VDD, while TS + VDS had higher GDNF and c-Ret expressions. VDD aggravates, and VDS ameliorates tic-like behavior in an IDPN-induced model. VDS may upregulate GDNF/c-Ret signaling activity through VDR, reversing the striatal DA decrease and alleviating tic-like behavior.
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Affiliation(s)
- Hong-Hua Li
- Department of Developmental and Behavioral Pediatrics, Children's Hospital, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
- School of Public Health, Jilin University, Changchun, Jilin Province, China
- The Child Health Clinical Research Center of Jilin Province, Changchun, China
| | - Xi-Fei Wang
- Department of Developmental and Behavioral Pediatrics, Children's Hospital, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
- The Child Health Clinical Research Center of Jilin Province, Changchun, China
| | - Bing Wang
- Department of Developmental and Behavioral Pediatrics, Children's Hospital, The First Hospital of Jilin University, Changchun, Jilin, 130021, China
- The Child Health Clinical Research Center of Jilin Province, Changchun, China
| | - Fei-Yong Jia
- Department of Developmental and Behavioral Pediatrics, Children's Hospital, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
- The Child Health Clinical Research Center of Jilin Province, Changchun, China.
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Vázquez-Lorente H, Herrera-Quintana L, Jiménez-Sánchez L, Fernández-Perea B, Plaza-Diaz J. Antioxidant Functions of Vitamin D and CYP11A1-Derived Vitamin D, Tachysterol, and Lumisterol Metabolites: Mechanisms, Clinical Implications, and Future Directions. Antioxidants (Basel) 2024; 13:996. [PMID: 39199241 PMCID: PMC11351441 DOI: 10.3390/antiox13080996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 08/11/2024] [Accepted: 08/17/2024] [Indexed: 09/01/2024] Open
Abstract
Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as improved immune, cardiovascular, and neurological functions as a result of chronic kidney disease and cancer. Additionally, supplementation with this vitamin has been shown to be one of the most cost-effective micronutrient interventions worldwide, highlighting its potential as a therapeutic approach. The underlying mechanisms and implications of this antioxidant function of vitamin D or CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites are not well understood. This comprehensive and narrative review is aimed at summarizing the current evidence regarding the molecular mechanisms implicated in this antioxidant function of vitamin D, as well as to provide a general overview and to identify key research areas for the future, offering an extensive perspective that can guide both researchers and clinicians in the management of diseases associated with oxidative stress and/or insufficient vitamin D status.
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Affiliation(s)
- Héctor Vázquez-Lorente
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (H.V.-L.); (L.H.-Q.); (L.J.-S.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Lourdes Herrera-Quintana
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (H.V.-L.); (L.H.-Q.); (L.J.-S.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
| | - Laura Jiménez-Sánchez
- Department of Physiology, Schools of Pharmacy and Medicine, University of Granada, 18071 Granada, Spain; (H.V.-L.); (L.H.-Q.); (L.J.-S.)
- Biomedical Research Center, Health Sciences Technology Park, University of Granada, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Beatriz Fernández-Perea
- Immunology and Clinical Analysis Service, Virgen de las Nieves University Hospital, 18014 Granada, Spain;
| | - Julio Plaza-Diaz
- Instituto de Investigación Biosanitaria IBS.GRANADA, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Children’s Hospital of Eastern Ontario Research Institute, Ottawa, ON K1H 8L1, Canada
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Sailike B, Onzhanova Z, Akbay B, Tokay T, Molnár F. Vitamin D in Central Nervous System: Implications for Neurological Disorders. Int J Mol Sci 2024; 25:7809. [PMID: 39063051 PMCID: PMC11277055 DOI: 10.3390/ijms25147809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 07/01/2024] [Accepted: 07/02/2024] [Indexed: 07/28/2024] Open
Abstract
Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain.
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Affiliation(s)
| | | | | | | | - Ferdinand Molnár
- Department of Biology, School of Sciences and Humanities, Nazarbayev University, Kabanbay Batyr 53, Astana 010000, Kazakhstan; (B.S.); (Z.O.); (B.A.); (T.T.)
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Wang R, Xu F, Xia X, Xiong A, Dai D, Ling Y, Sun R, Qiu L, Ding Y, Xie Z. The effect of vitamin D supplementation on primary depression: A meta-analysis. J Affect Disord 2024; 344:653-661. [PMID: 37852593 DOI: 10.1016/j.jad.2023.10.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 09/22/2023] [Accepted: 10/08/2023] [Indexed: 10/20/2023]
Abstract
BACKGROUND Previous meta-analyses reported inconsistent results on the effect of vitamin D on depression because of different baseline concentrations of 25-hydroxyvitamin D [25(OH)D], highlighting the need for a more accurate subgroup analysis of previously published findings. The goal of the present study was to evaluate the effect of vitamin D supplementation on depression in adults. METHODS A systematic search in numerous databases including PubMed, Embase, and Web of Science was performed. Randomized-controlled trials comparing the effect of vitamin D on depression in adults were selected. RESULTS Eighteen studies met the inclusion criteria in the retrieved citations. The meta-analysis showed that vitamin D supplementation had a significant effect on overall reduction in depression symptom scores (SMD = -0.15, 95 % CI [-0.26, -0.04]). Sub-group analysis showed that vitamin D supplementation significantly reduced depressive symptom scores in patients with serum 25(OH)D levels higher than 50 nmol/L (SMD = -0.38, 95 % CI [-0.68, -0.08]). CONCLUSIONS Vitamin D supplementation has a benefit on improving depressive symptoms in adults with primary depression and 25(OH)D levels higher than 50 nmol/L but has no effect on improving depressive symptoms in adults with primary depression and 25(OH)D levels lower than 50 nmol/L. Relatively high levels of 25(OH)D maybe required for alleviating depression. LIMITATIONS The randomized studies included in this study were designed and completed at different times and countries, the variability in duration and dose of vitamin D supplementation may have introduced significant heterogeneity and have militated against observation of the effects of vitamin D supplementation on depression.
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Affiliation(s)
- Rui Wang
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Feng Xu
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Xuedi Xia
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - An Xiong
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Dexing Dai
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Yali Ling
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Ruoman Sun
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Lei Qiu
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Ya Ding
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China
| | - Zhongjian Xie
- National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 139 Middle Renmin Road, Changsha 410011, Hunan, China.
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Tahir H, Munir N, Iqbal SS, Bacha U, Amir S, Umar H, Riaz M, Tahir IM, Ali Shah SM, Shafiq A, Akram M. Maternal vitamin D status and attention deficit hyperactivity disorder (ADHD), an under diagnosed risk factor; A review. EUR J INFLAMM 2023. [DOI: 10.1177/1721727x231161013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/04/2023] Open
Abstract
Vitamin D is important to mediate several brain processes such as proliferation, apoptosis, and neurotransmission in early stages of life. Vitamin D deficiency during critical periods of development can lead to persistent brain alterations. Vitamin D homeostasis during pregnancy is affected by two factors which includes an increase in mother’s calcitriol levels and an increase in mother’s Vitamin D Binding protein concentrations. Attention deficient hyperactivity disorder (ADHD) is an outcome of a complicated interaction between genetic, environmental, and developmental traits, and genetic factors cover about 80% of the cases. The efficiency of the immune system can be altered by a deficiency of Vitamin D in maternal body and maternal stress during gestation such as perinatal depression. Studies have proved that during gestation if there is a deficiency of vitamin D in maternal body, it can influence the brain development of the fetus and can also alter the synthesis of the brain-derived neurotropic factor. The current manuscript has been compiled to elaborate different factors which are associated with ADHD particularly focusing on the relationship of vitamin D deficiency in mothers. References material was selected from NCBI (PUBMED), Science direct, Google scholar, Publons etc. Using the terms ADHD, Vitamin D and Maternal nutritional status. Although, controversial relationship was found between the deficiency of Vitamin D level in pregnant women and development of ADHD in children but more controlled trials are required for future direction as well as to rule out other associated causes.
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Affiliation(s)
- Hafsa Tahir
- Department of Nutrition Sciences, School of Health Sciences, University of Management and Technology, Lahore, Pakistan
| | - Naveed Munir
- Department of Biomedical Lab Sciences, School of Health Sciences, University of Management and Technology, Lahore, Pakistan
| | - Syeda Saira Iqbal
- Knowledge Research and Support Services, University of Management and Technology, Lahore, Pakistan
| | - Umar Bacha
- Department of Nutrition Sciences, School of Health Sciences, University of Management and Technology, Lahore, Pakistan
| | - Saira Amir
- Department of Nutrition Sciences, School of Health Sciences, University of Management and Technology, Lahore, Pakistan
| | - Hassaan Umar
- School of Pharmaceutical Sciences, Universiti Sains, Malaysia
| | - Muhammad Riaz
- Department of Allied Health Sciences, Sargodha Medical College, University of Sargodha, Sargodha, Pakistan
| | - Imtiaz Mahmood Tahir
- College of Allied Health Professional, Directorate of Medical Sciences, Government College University‐Faisalabad, Faisalabad, Pakistan
| | - Syed Muhammad Ali Shah
- Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan
| | - Almina Shafiq
- Department of Biomedical Lab Sciences, School of Health Sciences, University of Management and Technology, Lahore, Pakistan
| | - Muhammad Akram
- Department of Eastern Medicine, Government College University Faisalabad, Faisalabad, Pakistan
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Jung J, Kang J, Kim T. Attenuation of homeostatic sleep response and rest-activity circadian rhythm in vitamin D deficient mice. Chronobiol Int 2023; 40:1097-1110. [PMID: 37661839 DOI: 10.1080/07420528.2023.2253299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 08/09/2023] [Accepted: 08/24/2023] [Indexed: 09/05/2023]
Abstract
The link between vitamin D deficiency (VDD) and sleep disturbances has long been suggested. However, the direct causality between VDD, sleep disturbances, and circadian rhythm remains unclear. We aimed to characterize sleep-wake behavior and circadian rhythms in an animal model of VDD. VDD was induced by feeding vitamin D-deficient chow, and we analyzed sleep and circadian rhythm parameters. During light period, VDD mice exhibited reduced wake with more frequent wake bouts and increased NREM sleep time. However, during dark period, the wake EEG power spectrum peaked at theta band frequency, and slow-wave energy was suppressed in mice with VDD. Rest-activity analyses revealed increased circadian period, lower wheel counts, and more frequent and short activity bouts during VDD. Combining sleep and circadian data, we found significantly suppressed activities during the hours with a wake duration shorter than 30 minutes. Moreover, mice in VDD state exhibited a negative correlation between wake theta power and hourly wheel-running counts during dark period. Our data point to a direct link between VDD and disturbances in sleep and rest-activity circadian rhythm, featuring frequent wake bouts during the sleeping phase, reduced sleep pressure build-up in dark period, and reduced activity levels due to increased susceptibility to sleepiness.
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Affiliation(s)
- Jieun Jung
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
| | - Jiseung Kang
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
| | - Tae Kim
- Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea
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11
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Mirarchi A, Albi E, Beccari T, Arcuri C. Microglia and Brain Disorders: The Role of Vitamin D and Its Receptor. Int J Mol Sci 2023; 24:11892. [PMID: 37569267 PMCID: PMC10419106 DOI: 10.3390/ijms241511892] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/17/2023] [Accepted: 07/23/2023] [Indexed: 08/13/2023] Open
Abstract
Accounting for 5-20% of the total glial cells present in the adult brain, microglia are involved in several functions: maintenance of the neural environment, response to injury and repair, immunesurveillance, cytokine secretion, regulation of phagocytosis, synaptic pruning, and sculpting postnatal neural circuits. Microglia contribute to some neurodevelopmental disorders, such as Nasu-Hakola disease (NHD), Tourette syndrome (TS), autism spectrum disorder (ASD), and schizophrenia. Moreover, microglial involvement in neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, has also been well established. During the last two decades, epidemiological and research studies have demonstrated the involvement of vitamin D3 (VD3) in the brain's pathophysiology. VD3 is a fat-soluble metabolite that is required for the proper regulation of many of the body's systems, as well as for normal human growth and development, and shows neurotrophic and neuroprotective actions and influences on neurotransmission and synaptic plasticity, playing a role in various neurological diseases. In order to better understand the exact mechanisms behind the diverse actions of VD3 in the brain, a large number of studies have been performed on isolated cells or tissues of the central nervous system (CNS). Here, we discuss the involvement of VD3 and microglia on neurodegeneration- and aging-related diseases.
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Affiliation(s)
- Alessandra Mirarchi
- Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy;
| | - Elisabetta Albi
- Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy; (E.A.); (T.B.)
| | - Tommaso Beccari
- Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy; (E.A.); (T.B.)
| | - Cataldo Arcuri
- Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy;
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12
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Ye X, Zhou Q, Ren P, Xiang W, Xiao L. The Synaptic and Circuit Functions of Vitamin D in Neurodevelopment Disorders. Neuropsychiatr Dis Treat 2023; 19:1515-1530. [PMID: 37424961 PMCID: PMC10327924 DOI: 10.2147/ndt.s407731] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 06/07/2023] [Indexed: 07/11/2023] Open
Abstract
Vitamin D deficiency/insufficiency is a public health issue around the world. According to epidemiological studies, low vitamin D levels have been associated with an increased risk of some neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). Animal models reveal that vitamin D has a variety of impacts on the synapses and circuits in the brain. A lack of vitamin D affects the expression of synaptic proteins, as well as the synthesis and metabolism of various neurotransmitters. Depending on where vitamin D receptors (VDRs) are expressed, vitamin D may also regulate certain neuronal circuits through the endocannabinoid signaling, mTOR pathway and oxytocin signaling. While inconsistently, some data suggest that vitamin D supplementation may be able to reduce the core symptoms of ASD and ADHD. This review emphasizes vitamin D's role in the synaptic and circuit mechanisms of neurodevelopmental disorders including ASD and ADHD. Future application of vitamin D in these disorders will depend on both basic research and clinical studies, in order to make the transition from the bench to the bedside.
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Affiliation(s)
- Xiaoshan Ye
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
| | - Qionglin Zhou
- International School of Public Health and One Health, Hainan Medical University, Haikou, People’s Republic of China
| | - Pengcheng Ren
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
- National Health Commission (NHC) Key Laboratory of Control of Tropical Diseases, Hainan Medical University, Haikou, People’s Republic of China
- School of Basic Medicine and Life Science, Hainan Medical University, Haikou, People’s Republic of China
| | - Wei Xiang
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
- National Health Commission (NHC) Key Laboratory of Control of Tropical Diseases, Hainan Medical University, Haikou, People’s Republic of China
| | - Le Xiao
- Hainan Women and Children’s Medical Center, School of Pediatrics, Hainan Medical University, Haikou, People’s Republic of China
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13
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Gezen-Ak D, Alaylıoğlu M, Yurttaş Z, Çamoğlu T, Şengül B, İşler C, Kına ÜY, Keskin E, Atasoy İL, Kafardar AM, Uzan M, Annweiler C, Dursun E. Vitamin D receptor regulates transcription of mitochondrial DNA and directly interacts with mitochondrial DNA and TFAM. J Nutr Biochem 2023; 116:109322. [PMID: 36963731 DOI: 10.1016/j.jnutbio.2023.109322] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 03/15/2023] [Accepted: 03/15/2023] [Indexed: 03/26/2023]
Abstract
Vitamin D receptor (VDR) is an essential transcription factor (TF) synthesized in different cell types. We hypothesized that VDR might also act as a mitochondrial TF. We conducted the experiments in primary cortical neurons, PC12, HEK293T, SH-SY5Y cell lines, human peripheral blood mononuclear cells (PBMC) and human brain. We showed that vitamin D/VDR affects the expression of mitochondrial DNA (mtDNA) encoded oxidative phosphorylation (OXPHOS) subunits. We observed the co-localization of VDR with mitochondria and the mtDNA with confocal microscopy. mtDNA-chromatin-immunoprecipitation and electrophoretic mobility shift assays indicated that VDR was able to bind to the mtDNA D-loop site in several locations, with a consensus sequence 'MMHKCA'. We also reported the possible interaction between VDR and mitochondrial transcription factor A (TFAM) and their binding sites located in close proximity in mtDNA. Consequently, our results showed for the first time that VDR was able to bind and regulate mtDNA transcription and interact with TFAM even in the human brain. These results not only revealed a novel function of VDR, but also showed that VDR is indispensable for energy demanded cells.
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Affiliation(s)
- Duygu Gezen-Ak
- Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Merve Alaylıoğlu
- Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Zuhal Yurttaş
- Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Tugay Çamoğlu
- Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Büşra Şengül
- Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Cihan İşler
- Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Neurosurgery
| | - Ümit Yaşar Kına
- Beykoz Institute of Life Sciences and Biotechnology, Bezmialem Vakif University, Istanbul, Turkey
| | - Ebru Keskin
- Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - İrem Lütfiye Atasoy
- Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ali Metin Kafardar
- Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Neurosurgery
| | - Mustafa Uzan
- Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Department of Neurosurgery
| | - Cedric Annweiler
- Department of Geriatric Medicine and Memory Clinic, Research Center on Autonomy and Longevity, University Hospital, Angers, France.; UPRES EA 4638, University of Angers, Angers, France.; Robarts Research Institute, Department of Medical Biophysics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
| | - Erdinç Dursun
- Brain and Neurodegenerative Disorders Research Laboratories, Department of Neuroscience, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey.
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14
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Janse A, van de Rest O, de Groot LCPGM, Witkamp RF. The Association of Vitamin D Status with Mild Cognitive Impairment and Dementia Subtypes: A Cross-Sectional Analysis in Dutch Geriatric Outpatients. J Alzheimers Dis 2023; 91:1359-1369. [PMID: 36641667 DOI: 10.3233/jad-220732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Vitamin D deficiency is associated with all-cause dementia and Alzheimer's disease (AD). At the same time, this knowledge is limited specifically for vascular dementia (VaD), while data regarding other subtypes of dementia are even more limited. OBJECTIVE To investigate the association of 25-hydroxy vitamin D (25(OH)D) status with dementia subtypes in an outpatient geriatric population. METHODS In a cross-sectional design, we analyzed data from 1,758 patients of an outpatient memory clinic in The Netherlands. Cognitive disorders were diagnosed by a multidisciplinary team according to international clinical standards. At each first-visit 25(OH)D levels were measured. Data were analyzed using ANCOVA in four models with age, gender, BMI, education, alcohol, smoking, season, polypharmacy, calcium, eGFR, and glucose as co-variates. 25(OH)D was treated as a continuous square rooted (sqr) variable. RESULTS In the fully adjusted model, reduced 25(OH)D serum levels (sqr) were found in AD (estimated mean 7.77±0.11 CI95% 7.55-7.99): and in VaD (estimated mean 7.60±0.16 CI95% 7.28-7.92) patients compared to no-dementia (ND) patients (estimated mean 8.27±0.09 CI95% 8.10-8.45) (ND-AD: p = 0.006, CI95% 0.08-0.92.; ND-VaD p = 0.004 CI95% 0.13-1.22). We did not find differences in 25(OH)D levels of mild cognitive impairment (MCI) or other dementia patients compared to ND patients, nor differences in comparing dementia subtypes. CONCLUSION We observed significantly lower 25(OH)D serum levels in both AD and VaD patients compared to no-dementia patients, but no significant differences between MCI and Lewy body and mixed dementia subtypes in this cross-sectional study of a geriatric outpatient clinic population.
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Affiliation(s)
- André Janse
- Division of Human Nutrition and Health, Wageningen University & Research, the Netherlands.,Department of Geriatric Medicine, Gelderse Vallei Hospital, the Netherlands
| | - Ondine van de Rest
- Division of Human Nutrition and Health, Wageningen University & Research, the Netherlands
| | | | - Renger F Witkamp
- Division of Human Nutrition and Health, Wageningen University & Research, the Netherlands
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15
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Gezen-Ak D, Dursun E. Vitamin D, a Secosteroid Hormone and Its Multifunctional Receptor, Vitamin D Receptor, in Alzheimer's Type Neurodegeneration. J Alzheimers Dis 2023; 95:1273-1299. [PMID: 37661883 DOI: 10.3233/jad-230214] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
Vitamin D is a secosteroid hormone exerting neurosteroid-like properties. Its well-known nuclear hormone receptor, and recently proposed as a mitochondrial transcription factor, vitamin D receptor, acts for its primary functions. The second receptor is an endoplasmic reticulum protein, protein disulfide isomerase A3 (PDIA3), suggested to act as a rapid response. Vitamin D has effects on various systems, particularly through calcium metabolism. Among them, the nervous system has an important place in the context of our subject. Recent studies have shown that vitamin D and its receptors have numerous effects on the nervous system. Neurodegeneration is a long-term process. Throughout a human life span, so is vitamin D deficiency. Our previous studies and others have suggested that the out-come of long-term vitamin D deficiency (hypovitaminosis D or inefficient utilization of vitamin D), may lead neurons to be vulnerable to aging and neurodegeneration. We suggest that keeping vitamin D levels at adequate levels at all stages of life, considering new approaches such as agonists that can activate vitamin D receptors, and utilizing other derivatives produced in the synthesis process with UVB are crucial when considering vitamin D-based intervention studies. Given most aspects of vitamin D, this review outlines how vitamin D and its receptors work and are involved in neurodegeneration, emphasizing Alzheimer's disease.
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Affiliation(s)
- Duygu Gezen-Ak
- Department of Neuroscience, Brain and Neurodegenerative Disorders Research Laboratories, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Erdinc Dursun
- Department of Neuroscience, Brain and Neurodegenerative Disorders Research Laboratories, Institute of Neurological Sciences, Istanbul University-Cerrahpasa, Istanbul, Turkey
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16
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Wang W, Li Y, Meng X. Vitamin D and neurodegenerative diseases. Heliyon 2023; 9:e12877. [PMID: 36820164 PMCID: PMC9938420 DOI: 10.1016/j.heliyon.2023.e12877] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 11/23/2022] [Accepted: 01/05/2023] [Indexed: 01/13/2023] Open
Abstract
Neurodegenerative diseases, featured by progressive loss of structure or function of neurons, are considered incurable at present. Movement disorders like tremor and postural instability, cognitive or behavioral disorders such as memory impairment are the most common symptoms of them and the growing patient population of neurodegenerative diseases poses a serious threat to public health and a burden on economic development. Hence, it is vital to prevent the occurrence of the diseases and delay their progress. Vitamin D can be transformed into a hormone in vivo with both genomic and non-genomic actions, exerting diverse physiological effects. Cumulative evidence indicates that vitamin D can ameliorate neurodegeneration by regulating pertinent molecules and signaling pathways including maintaining Ca2+ homeostasis, reducing oxidative stress, inhibiting inflammation, suppressing the formation and aggregation of the pathogenic protein, etc. This review updates discoveries of molecular mechanisms underlying biological functions of vitamin D in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and vascular dementia. Clinical trials investigating the influence of vitamin D supplementation in patients with neurodegenerative diseases are also summarized. The synthesized information will probably provoke an enhanced understanding of the neuroprotective roles of vitamin D in the nervous system and provide therapeutic options for patients with neurodegenerative diseases in the future.
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17
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Behl T, Arora A, Singla RK, Sehgal A, Makeen HA, Albratty M, Meraya AM, Najmi A, Bungau SG. Understanding the role of "sunshine vitamin D " in Parkinson's disease: A review. Front Pharmacol 2022; 13:993033. [PMID: 36601055 PMCID: PMC9807223 DOI: 10.3389/fphar.2022.993033] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022] Open
Abstract
Next to Alzheimer's disease, Parkinson's disease constitutes the second most widespread neurological disorder, primarily affecting the older population. Its symptoms are noticeable with advancing age including tremors, postural imbalance, and slow movements, and over time, these symptoms get aggravated, progressing to osteoporosis, osteopenia, and risk of fractures. These symptoms correlate to low bone density and hence weakened bones; thus, vitamin D proves to be an intricate component of the pathogenesis of the disease. Moreover, lower serum concentrations of vitamin D have been found in diseased subjects. Supplementation with vitamin D can retard the aggravation of non-motor as well as motor symptoms of Parkinson's disease that include cognitive improvement along with the decline in risk of fractures. Also, vitamin D is extremely crucial for brain functioning, targeting dopaminergic neurons, and almost the entire functioning of the brain is affected. However, further exploration is required to determine the toxic dose of vitamin D in Parkinson's subjects. This "sunshine vitamin" surely can be a ray of sunshine for neurologically diseased subjects.
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Affiliation(s)
- Tapan Behl
- School of Health Science and Technology, University of Petroleum and Energy Studies, Bidholi, Uttarakhand, India
| | - Arpita Arora
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Rajeev K. Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Aayush Sehgal
- GHG Khalsa College of Pharmacy, Gurusar Sadhar, Ludhiana, Punjab, India
| | - Hafiz A. Makeen
- Pharmacy Practice Research Unit, Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Mohammed Albratty
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Abdulkarim M. Meraya
- Pharmacy Practice Research Unit, Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Asim Najmi
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Simona Gabriela Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
- Doctoral School of Biomedical Sciences, University of Oradea, Oradea, Romania
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18
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Rihal V, Khan H, Kaur A, Singh TG, Abdel-Daim MM. Therapeutic and mechanistic intervention of vitamin D in neuropsychiatric disorders. Psychiatry Res 2022; 317:114782. [PMID: 36049434 DOI: 10.1016/j.psychres.2022.114782] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 08/08/2022] [Accepted: 08/09/2022] [Indexed: 11/19/2022]
Abstract
Vitamin D deficiency is believed to affect between 35 and 55% of the world's population, making it a hidden pandemic. In addition to its role in bone and calcium homeostasis, vitamin D has also been linked in preclinical and clinical research to brain function. These outcomes have also been used for a variety of neuropsychiatric and neurodevelopmental problems. Nevertheless, these individuals are more prone to develop signs of cognitive decline. This review will emphasize the association between vitamin D and neuropsychiatric illnesses such as autism, schizophrenia, depression, and Attention Deficit Hyperactivity Disorder (ADHD). While numerous research show vitamin D's essential role in cognitive function in neuropsychiatric illnesses, it is too early to propose its effect on cognitive symptoms with certainty. It is necessary to conduct additional research into the associations between vitamin D deficiency and cognitive abnormalities, particularly those found in autism, schizophrenia, depression, and ADHD, to develop initiatives that address the pressing need for novel and effective preventative therapeutic strategies.
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Affiliation(s)
- Vivek Rihal
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Heena Khan
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Amarjot Kaur
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | | | - Mohamed M Abdel-Daim
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231 Jeddah 21442, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
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19
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Albiñana C, Boelt SG, Cohen AS, Zhu Z, Musliner KL, Vilhjálmsson BJ, McGrath JJ. Developmental exposure to vitamin D deficiency and subsequent risk of schizophrenia. Schizophr Res 2022; 247:26-32. [PMID: 34247885 DOI: 10.1016/j.schres.2021.06.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Revised: 06/01/2021] [Accepted: 06/04/2021] [Indexed: 01/22/2023]
Abstract
Over the last half century, a body of convergent evidence has accumulated linking disruption of early brain development with an increased risk of mental disorders, including schizophrenia. The orderly cascade of brain development may be disrupted by exposure to suboptimal concentrations of a range of biological substrates and micronutrients. We hypothesized that those exposed to vitamin D deficiency during early life, have an increased risk of neurodevelopmental disorders, including schizophrenia. The hypothesis was based on the link between an increased risk of schizophrenia in (a) those born in winter and spring, when vitamin D deficiency is more prevalent, and (b) the offspring of dark-skinned migrants living in cold climates, who have a markedly increased risk of vitamin D deficiency. In this review, we summarize evidence from analytic epidemiology related to this hypothesis. Two case-control studies based on Danish neonatal dried blood spots have found that neonatal vitamin deficiency is associated with an increased risk of schizophrenia. However, recent genetic analyses have also suggested that common variants linked to schizophrenia may lead to lower vitamin D concentrations (possibly mediated via reduced outdoor activity). We summarize limitations of the current evidence and outline suggestions that can guide future research. Based on currently available data, there is insufficient evidence to support public health recommendations related to this topic. However, we cannot reject the hypothesis that the provision of vitamin D supplementation to pregnant women and/or offspring in groups vulnerable to vitamin D deficiency may subsequently reduce the incidence of schizophrenia in the offspring.
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Affiliation(s)
- Clara Albiñana
- National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH - the Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
| | | | - Arieh S Cohen
- Department of Inherited Diseases, Statens Serum Institut, Copenhagen, Denmark
| | - Zhihong Zhu
- National Centre for Register-based Research, Aarhus University, Aarhus, Denmark
| | - Katherine L Musliner
- National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH - the Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
| | - Bjarni J Vilhjálmsson
- National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; iPSYCH - the Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
| | - John J McGrath
- National Centre for Register-based Research, Aarhus University, Aarhus, Denmark; Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Wacol, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Australia.
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20
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khan B, Shafiq H, Abbas S, Jabeen S, Khan SA, Afsar T, Almajwal A, Alruwaili NW, al-disi D, Alenezi S, Parveen Z, Razak S. Vitamin D status and its correlation to depression. Ann Gen Psychiatry 2022; 21:32. [PMID: 35982462 PMCID: PMC9389668 DOI: 10.1186/s12991-022-00406-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 07/13/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression. METHODS Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects. RESULTS Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency. CONCLUSIONS The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression.
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Affiliation(s)
- Bashir khan
- Institute of Basic Medical Sciences, Khyber Medical University Peshawar, Peshawar, Pakistan
| | - Huma Shafiq
- Institute of Cellular Medicine, Newcastle University Medical School, Newcastle University United Kingdom, Newcastle, England
| | - Seyyedha Abbas
- Institute of Basic Medical Sciences, Khyber Medical University Peshawar, Peshawar, Pakistan
| | - Summeira Jabeen
- Institute of Basic Medical Sciences, Khyber Medical University Peshawar, Peshawar, Pakistan
| | - Sikandar Ali Khan
- Institute of Basic Medical Sciences, Khyber Medical University Peshawar, Peshawar, Pakistan
| | - Tayyaba Afsar
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ali Almajwal
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Nawaf W. Alruwaili
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Dara al-disi
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Sultan Alenezi
- Institute of Cellular Medicine, Newcastle University Medical School, Newcastle University United Kingdom, Newcastle, England
| | | | - Suhail Razak
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
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21
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Kouba BR, Camargo A, Gil-Mohapel J, Rodrigues ALS. Molecular Basis Underlying the Therapeutic Potential of Vitamin D for the Treatment of Depression and Anxiety. Int J Mol Sci 2022; 23:ijms23137077. [PMID: 35806075 PMCID: PMC9266859 DOI: 10.3390/ijms23137077] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Revised: 06/22/2022] [Accepted: 06/24/2022] [Indexed: 02/07/2023] Open
Abstract
Major depressive disorder and anxiety disorders are common and disabling conditions that affect millions of people worldwide. Despite being different disorders, symptoms of depression and anxiety frequently overlap in individuals, making them difficult to diagnose and treat adequately. Therefore, compounds capable of exerting beneficial effects against both disorders are of special interest. Noteworthily, vitamin D deficiency has been associated with an increased risk of developing depression and anxiety, and individuals with these psychiatric conditions have low serum levels of this vitamin. Indeed, in the last few years, vitamin D has gained attention for its many functions that go beyond its effects on calcium–phosphorus metabolism. Particularly, antioxidant, anti-inflammatory, pro-neurogenic, and neuromodulatory properties seem to contribute to its antidepressant and anxiolytic effects. Therefore, in this review, we highlight the main mechanisms that may underlie the potential antidepressant and anxiolytic effects of vitamin D. In addition, we discuss preclinical and clinical studies that support the therapeutic potential of this vitamin for the management of these disorders.
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Affiliation(s)
- Bruna R. Kouba
- Center of Biological Sciences, Department of Biochemistry, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil; (B.R.K.); (A.C.)
| | - Anderson Camargo
- Center of Biological Sciences, Department of Biochemistry, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil; (B.R.K.); (A.C.)
| | - Joana Gil-Mohapel
- Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC V8P 5C2, Canada
- Correspondence: (J.G.-M.); (A.L.S.R.); Tel.: +1-250-721-6586 (J.G.-M.); +55-(48)-3721-5043 (A.L.S.R.)
| | - Ana Lúcia S. Rodrigues
- Center of Biological Sciences, Department of Biochemistry, Federal University of Santa Catarina, Florianópolis 88040-900, SC, Brazil; (B.R.K.); (A.C.)
- Correspondence: (J.G.-M.); (A.L.S.R.); Tel.: +1-250-721-6586 (J.G.-M.); +55-(48)-3721-5043 (A.L.S.R.)
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22
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Gombash SE, Lee PW, Sawdai E, Lovett-Racke AE. Vitamin D as a Risk Factor for Multiple Sclerosis: Immunoregulatory or Neuroprotective? Front Neurol 2022; 13:796933. [PMID: 35651353 PMCID: PMC9149265 DOI: 10.3389/fneur.2022.796933] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 04/13/2022] [Indexed: 12/18/2022] Open
Abstract
Vitamin D insufficiency during childhood has been linked to the development of multiple sclerosis (MS), typically an adult-onset inflammatory demyelinating disease of the central nervous system (CNS). Since vitamin D was known to have immunoregulatory properties on both innate and adaptive immunity, it was hypothesized that low vitamin D resulted in aberrant immune responses and the development of MS. However, vitamin D receptors are present on many cell types, including neurons, oligodendrocytes, astrocytes and microglia, and vitamin D has profound effects on development and function of the CNS. This leads to the possibility that low vitamin D may alter the CNS in a manner that makes it vulnerable to inflammation and the development of MS. This review analysis the role of vitamin D in the immune and nervous system, and how vitamin D insufficiency in children may contribute to the development of MS.
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Affiliation(s)
- Sara E Gombash
- Department of Neuroscience, The Ohio State University, Columbus, OH, United States
| | - Priscilla W Lee
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States
| | - Elizabeth Sawdai
- Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States
| | - Amy E Lovett-Racke
- Department of Neuroscience, The Ohio State University, Columbus, OH, United States.,Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, United States
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23
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Gázquez A, Sánchez-Campillo M, Barranco A, Rueda R, Chan JP, Kuchan MJ, Larqué E. Calcifediol During Pregnancy Improves Maternal and Fetal Availability of Vitamin D Compared to Vitamin D3 in Rats and Modifies Fetal Metabolism. Front Nutr 2022; 9:871632. [PMID: 35495908 PMCID: PMC9040672 DOI: 10.3389/fnut.2022.871632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 03/14/2022] [Indexed: 11/26/2022] Open
Abstract
The fetus depends on the transplacental transfer of vitamin D. Calcifediol (25-OH-D3) is the vitamin D metabolite that crosses the placenta. Previously, oral 25-OH-D3 improved serum 25-OH-D3 compared to vitamin D3 in non-pregnant subjects, although no studies are available in pregnant women. We evaluated the availability of oral 25-OH-D3 compared to vitamin D3 during pregnancy, as well as, their levels in the fetus and effect on metabolism-related proteins. Twenty female rats per group were fed with 25 μg/kg of diet of vitamin D3 (1,000 UI vitamin D/kg diet) or with 25 μg/kg diet of 25-OH-D3. We analyzed 25-OH-D3 levels in maternal and fetal plasma; protein levels of vitamin D receptor (VDR), fatty acid translocase (FAT), and scavenger-receptor class B type-1 (SR-B1) in both maternal liver and placenta; and protein levels of VDR and Glutamate decarboxylase (GAD67) in fetal brain. 25-OH-D3 doubled the concentration of 25-OH-D3 in both maternal and fetal plasma compared to vitamin D3. In addition, maternal liver VDR, FAT, and SR-BI increased significantly in the 25-OH-D3 group, but no changes were found in the placenta. Interestingly, 25-OH-D3 decreased GAD67 expression in the fetal brain and it also tended to decrease VDR (P = 0.086). In conclusion, 25-OH-D3 provided better vitamin D availability for both mother and fetus when administered during pregnancy compared to vitamin D3. No adverse effects on pregnancy outcomes were observed. The effects of 25-OH-D3 on the expression of VDR and GAD67 in fetal brain require further investigation.
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Affiliation(s)
- Antonio Gázquez
- Department of Animal Physiology, School of Biology, University of Murcia, Murcia, Spain
| | | | - Alejandro Barranco
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, Granada, Spain
| | - Ricardo Rueda
- Research and Development Department, Abbott Nutrition SL, Granada, Spain
| | - Jia P. Chan
- Research and Development Department, Abbott Nutrition SL, Singapore, Singapore
| | - Matthew J. Kuchan
- Research and Development Department, Abbott Nutrition SL, Columbus, OH, United States
| | - Elvira Larqué
- Department of Animal Physiology, School of Biology, University of Murcia, Murcia, Spain
- *Correspondence: Elvira Larqué,
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Bouillon R, Antonio L, Olarte OR. Calcifediol (25OH Vitamin D3) Deficiency: A Risk Factor from Early to Old Age. Nutrients 2022; 14:nu14061168. [PMID: 35334824 PMCID: PMC8949915 DOI: 10.3390/nu14061168] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/02/2022] [Accepted: 03/07/2022] [Indexed: 02/04/2023] Open
Abstract
Vitamin D deficiency is the main cause of nutritional rickets in children and osteomalacia in adults. There is consensus that nutritional access to vitamin D can be estimated by measuring serum concentrations of 25OHD and vitamin D deficiency can thus be considered as calcifediol deficiency. However, the threshold for vitamin D/calcifediol sufficiency remains a matter of debate. Vitamin D/calcifediol deficiency has been associated with musculoskeletal effects but also multiple adverse extra-skeletal consequences. If these consequences improve or if they can be treated with vitamin D supplementation is still unclear. Observational studies suggest a higher infection risk in people with low calcifediol levels. There is also a consistent association between serum calcifediol and cardiovascular events and deaths, but large-scale, long-term intervention studies did not show any benefit on cardiovascular outcomes from supplementation, at least not in subjects without clear vitamin D deficiency. Cancer risk also did not change with vitamin D treatment, although there are some data that higher serum calcifediol is associated with longer survival in cancer patients. In pregnant women, vitamin D supplementation decreases the risk of pre-eclampsia, gestational diabetes mellitus, and low birth weight. Although preclinical studies showed that the vitamin D endocrine system plays a role in certain neural cells as well as brain structure and function, there is no evidence to support a beneficial effect of vitamin D in neurodegenerative diseases. Vitamin D supplementation may marginally affect overall mortality risk especially in elderly subjects with low serum calcifediol concentrations.
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Affiliation(s)
- Roger Bouillon
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, 3000 Leuven, Belgium;
- Correspondence:
| | - Leen Antonio
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, 3000 Leuven, Belgium;
- Department of Endocrinology, University Hospitals Leuven, 3000 Leuven, Belgium
| | - Oscar Rosero Olarte
- Clinical Endocrinology, Asociación Colombiana de Osteoporosis, Bogotá 500005, Colombia;
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Janjusevic M, Gagno G, Fluca AL, Padoan L, Beltrami AP, Sinagra G, Moretti R, Aleksova A. The peculiar role of vitamin D in the pathophysiology of cardiovascular and neurodegenerative diseases. Life Sci 2022; 289:120193. [PMID: 34864062 DOI: 10.1016/j.lfs.2021.120193] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 11/24/2021] [Accepted: 11/29/2021] [Indexed: 02/07/2023]
Abstract
Vitamin D is a hormone with both genomic and non-genomic actions. It exerts its activity by binding vitamin D receptor (VDR), which belongs to the superfamily of nuclear receptors and ligand-activated transcription factors. Since VDR has been found in various tissues, it has been estimated that it regulates approximately 3% of the human genome. Several recent studies have shown pleiotropic effects of vitamin D in various processes such as cellular proliferation, differentiation, DNA repair and apoptosis and its involvement in different pathophysiological conditions as inflammation, diabetes mellitus, and anemia. It has been suggested that vitamin D could play an important role in neurodegenerative and cardiovascular disorders. Moderate to strong associations between lower serum vitamin D concentrations and stroke and cardiovascular events have been identified in different analytic approaches, even after controlling for traditional demographic and lifestyle covariates. The mechanisms behind the associations between vitamin D and cerebrovascular and cardiologic profiles have been widely examined both in animal and human studies. Optimization of vitamin D levels in human subjects may improve insulin sensitivity and beta-cell function and lower levels of inflammatory markers. Moreover, it has been demonstrated that altered gene expression of VDR and 1,25D3-membrane-associated rapid response steroid-binding (1,25D3-MARRS) receptor influences the role of vitamin D within neurons and allows them to be more prone to degeneration. This review summarizes the current understanding of the molecular mechanisms underlying vitamin D signaling and the consequences of vitamin D deficiency in neurodegenerative and cardiovascular disorders.
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Affiliation(s)
- Milijana Janjusevic
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Giulia Gagno
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Alessandra Lucia Fluca
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Laura Padoan
- Cardiology and Cardiovascular Physiopathology, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, 06156 Perugia, Italy
| | - Antonio Paolo Beltrami
- Clinical Pathology Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC) and Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
| | - Gianfranco Sinagra
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Rita Moretti
- Department of Internal Medicine and Neurology, Neurological Clinic, Complex Case Section, Trieste, Italy
| | - Aneta Aleksova
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy.
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Dell’Isola GB, Tulli E, Sica R, Vinti V, Mencaroni E, Di Cara G, Striano P, Verrotti A. The Vitamin D Role in Preventing Primary Headache in Adult and Pediatric Population. J Clin Med 2021; 10:jcm10245983. [PMID: 34945279 PMCID: PMC8709239 DOI: 10.3390/jcm10245983] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/17/2021] [Accepted: 12/17/2021] [Indexed: 12/11/2022] Open
Abstract
Headache is among the main neurological disorders with a great impact on both adults and children. The diagnosis of primary headache and proper management is often delayed with a great impact on work productivity and overall quality of life. Chronic headache often requires prophylactic therapy to reduce the frequency and severity of the attacks and the use of abortive medications. Besides the use of several classes of drugs, another treatment modality is the use of Nutraceuticals. Some studies have suggested a possible role of vitamin D in headache prophylaxis. Indeed, vitamin D is involved in several pathways of brain development, neuroprotection and neurotransmission. Moreover, there is data suggesting a close relationship between primary headache and vitamin D deficiency, both in children and in adults. To date, a few studies have evaluated the effect of vitamin D on headaches. The aim of this review is to summarize the data collected on headache prophylaxis with vitamin D comparing the effects of vitamin D in pediatric and adult populations.
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Affiliation(s)
- Giovanni Battista Dell’Isola
- Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129 Perugia, Italy; (E.T.); (R.S.); (V.V.); (E.M.); (G.D.C.); (A.V.)
- Correspondence:
| | - Eleonora Tulli
- Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129 Perugia, Italy; (E.T.); (R.S.); (V.V.); (E.M.); (G.D.C.); (A.V.)
| | - Rossella Sica
- Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129 Perugia, Italy; (E.T.); (R.S.); (V.V.); (E.M.); (G.D.C.); (A.V.)
| | - Valerio Vinti
- Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129 Perugia, Italy; (E.T.); (R.S.); (V.V.); (E.M.); (G.D.C.); (A.V.)
| | - Elisabetta Mencaroni
- Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129 Perugia, Italy; (E.T.); (R.S.); (V.V.); (E.M.); (G.D.C.); (A.V.)
| | - Giuseppe Di Cara
- Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129 Perugia, Italy; (E.T.); (R.S.); (V.V.); (E.M.); (G.D.C.); (A.V.)
| | - Pasquale Striano
- Pediatric Neurology and Muscular Diseases Unit, IRCCS “G. Gaslini” Institute, Gerolamo Gaslini Street, 5, 16147 Genoa, Italy;
- Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Paolo Daneo Square, 3, 16132 Genoa, Italy
| | - Alberto Verrotti
- Department of Pediatrics, University of Perugia, Giorgio Menghini Square, 06129 Perugia, Italy; (E.T.); (R.S.); (V.V.); (E.M.); (G.D.C.); (A.V.)
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Bahrami A, Rezaeitalab F, Farahmand SK, Mazloum Khorasani Z, Arabi SM, Bahrami-Taghanaki H, Ferns GA, Ghayour-Mobarhan M. High-dose Vitamin D Supplementation and Improvement in Cognitive Abilities, Insomnia, and Daytime Sleepiness in Adolescent Girls. Basic Clin Neurosci 2021; 12:339-348. [PMID: 34917293 PMCID: PMC8666927 DOI: 10.32598/bcn.2021.1910.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 07/10/2019] [Accepted: 09/02/2020] [Indexed: 11/20/2022] Open
Abstract
Introduction: Vitamin D may affect the modulation of signaling pathways in the central nervous system. We aimed to evaluate the effect of high-dose vitamin D supplementation on neuropsychological functions in female adolescents. Methods: We studied the effects of 9 weeks of vitamin D supplementation (50000 IU vitamin D3 [cholecalciferol]/week) on cognitive abilities and sleep disorders in 940 adolescent girls. Results: Oral vitamin D supplementation improved cognitive abilities, including memory, inhibitory control, selective attention, decision making, planning, sustained attention, and cognitive flexibility in healthy adolescent girls (P<0.001). The prevalence of subjects with insomnia after intervention fell from 15.0% to 11.3%. Similar results were also found for the prevalence of sleepiness (15.6% reduced to 14.7%), or cases with both insomnia and sleepiness (8.0% reduced to 6.1%; P<0.05). Conclusion: High dose of vitamin D can improve cognitive abilities and alleviate insomnia and daytime sleepiness in adolescent girls. Further investigations are required on different population groups (age and gender) to determine the sustainability of these effects. The value of vitamin D therapy in other neurological disorders would also be of research interest.
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Affiliation(s)
- Afsane Bahrami
- Cellular and Molecular Research Center, School of Medicine, Birjand University of Medical Sciences, Bijand, Iran
| | - Fariborz Rezaeitalab
- Department of Neurology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Kazem Farahmand
- Department of Traditional Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Mazloum Khorasani
- Endocrine Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mostafa Arabi
- Biochemistry of Nutrition Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamidreza Bahrami-Taghanaki
- Chinese and Complementary Medicine Research Center, School of Traditional and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, School of Brighton & Sussex Medical, University of Brighton and the University of Sussex, Falmer, Brighton, Sussex, UK
| | - Majid Ghayour-Mobarhan
- Metabolic Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Nema J, Randhir K, Wadhwani N, Sundrani D, Joshi S. Maternal vitamin D deficiency reduces docosahexaenoic acid, placental growth factor and peroxisome proliferator activated receptor gamma levels in the pup brain in a rat model of preeclampsia. Prostaglandins Leukot Essent Fatty Acids 2021; 175:102364. [PMID: 34768025 DOI: 10.1016/j.plefa.2021.102364] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 10/01/2021] [Accepted: 10/27/2021] [Indexed: 12/26/2022]
Abstract
BACKGROUND Preeclampsia is a pregnancy disorder characterized with abnormal placental angiogenesis. Vitamin D and long chain polyunsaturated fatty acids (LCPUFA) play a crucial role in pregnancy and are required for normal placental and fetal growth and development. This study reports the effect of maternal vitamin D on LCPUFA levels in the mother and offspring brain fatty acid levels and angiogenic markers in a rat model of preeclampsia. METHODS Female rats were divided into four groups from pre-pregnancy to pregnancy, viz Control; Preeclampsia (PE); Vitamin D deficient with PE (VDD-PE) and Vitamin D supplemented with PE (VDS-PE). Preeclampsia was induced by administering l-nitroarginine methyl ester (L-NAME) at the dose of 50 mg/kg body weight/day from day 14 to day 19 of gestation. Dams were sacrificed at d20 of gestation to collect dam blood, placenta and pup brain. LCPUFA levels from dam plasma, erythrocytes and placenta and its transcription factor peroxisome proliferator activated receptor gamma (PPAR-g) from placenta were estimated. Pup brain LCPUFA levels, angiogenic factors vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and transcription factor hypoxia inducible factor (Hif-1α) and PPAR-g were also estimated. RESULTS Maternal vitamin D status influences fatty acid levels. Placental PPAR-g levels were lower in the VDD-PE group as compared to the VDS-PE groups (p < 0.01). In the offspring brain, both PE and VDD-PE group showed lower levels of DHA (p < 0.05 for both) while saturated fatty acids (SFA) levels in the VDD-PE group were higher as compared to the control group (p < 0.05). VDD-PE group also showed lower levels of PlGF and PPAR-g (p < 0.01 and p < 0.05, respectively) in the pup brain while vitamin D supplementation demonstrated levels similar to control. CONCLUSION This study for the first time demonstrates that maternal vitamin D status influences LCPUFA metabolism and angiogenesis in the offspring brain.
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Affiliation(s)
- Juhi Nema
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Karuna Randhir
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Nisha Wadhwani
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Deepali Sundrani
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India
| | - Sadhana Joshi
- Mother and Child Health, Interactive Research School for Health Affairs (IRSHA), Bharati Vidyapeeth (Deemed to be University), Pune, India.
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Gáll Z, Székely O. Role of Vitamin D in Cognitive Dysfunction: New Molecular Concepts and Discrepancies between Animal and Human Findings. Nutrients 2021; 13:nu13113672. [PMID: 34835929 PMCID: PMC8620681 DOI: 10.3390/nu13113672] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 10/13/2021] [Accepted: 10/18/2021] [Indexed: 12/12/2022] Open
Abstract
PURPOSE OF REVIEW increasing evidence suggests that besides the several metabolic, endocrine, and immune functions of 1alpha,25-dihydroxyvitamin D (1,25(OH)2D), the neuronal effects of 1,25(OH)2D should also be considered an essential contributor to the development of cognition in the early years and its maintenance in aging. The developmental disabilities induced by vitamin D deficiency (VDD) include neurological disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia) characterized by cognitive dysfunction. On the other hand, VDD has frequently been associated with dementia of aging and neurodegenerative diseases (e.g., Alzheimer's, Parkinson's disease). RECENT FINDINGS various cells (i.e., neurons, astrocytes, and microglia) within the central nervous system (CNS) express vitamin D receptors (VDR). Moreover, some of them are capable of synthesizing and catabolizing 1,25(OH)2D via 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) and 25-hydroxyvitamin D 24-hydroxylase (CYP24A1) enzymes, respectively. Both 1,25(OH)2D and 25-hydroxyvitamin D were determined from different areas of the brain and their uneven distribution suggests that vitamin D signaling might have a paracrine or autocrine nature in the CNS. Although both cholecalciferol and 25-hydroxyvitamin D pass the blood-brain barrier, the influence of supplementation has not yet demonstrated to have a direct impact on neuronal functions. So, this review summarizes the existing evidence for the action of vitamin D on cognitive function in animal models and humans and discusses the possible pitfalls of therapeutic clinical translation.
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Affiliation(s)
- Zsolt Gáll
- Department of Pharmacology and Clinical Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, 540142 Târgu Mureș, Romania
- Correspondence:
| | - Orsolya Székely
- Department of Nephrology/Internal Medicine, Mures County Clinical Hospital, 540103 Târgu Mureș, Romania;
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30
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Vitamin D Status and Cognitive and Functional Outcomes in Patients With Traumatic Brain Injury. TOP CLIN NUTR 2021. [DOI: 10.1097/tin.0000000000000256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Chang Villacreses MM, Karnchanasorn R, Panjawatanan P, Ou HY, Chiu KC. Conundrum of vitamin D on glucose and fuel homeostasis. World J Diabetes 2021; 12:1363-1385. [PMID: 34630895 PMCID: PMC8472505 DOI: 10.4239/wjd.v12.i9.1363] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 05/10/2021] [Accepted: 08/05/2021] [Indexed: 02/06/2023] Open
Abstract
As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.
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Affiliation(s)
- Maria Mercedes Chang Villacreses
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
| | - Rudruidee Karnchanasorn
- Division of Endocrinology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, United States
| | - Panadeekarn Panjawatanan
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY 13326, United States
| | - Horng-Yih Ou
- Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan 700, Taiwan
| | - Ken C Chiu
- Department of Clinical Diabetes, Endocrinology, and Metabolism, City of Hope National Medical Center, Duarte, CA 91010, United States
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Harbor-UCLA Medical Center, Torrance, CA 90509, United States
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Murdaca G, Banchero S, Tonacci A, Nencioni A, Monacelli F, Gangemi S. Vitamin D and Folate as Predictors of MMSE in Alzheimer's Disease: A Machine Learning Analysis. Diagnostics (Basel) 2021; 11:940. [PMID: 34073931 PMCID: PMC8225187 DOI: 10.3390/diagnostics11060940] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 05/21/2021] [Accepted: 05/23/2021] [Indexed: 12/13/2022] Open
Abstract
Vitamin D (VD) and micronutrients, including folic acid, are able to modulate both the innate and the adaptive immune responses. Low VD and folic acid levels appear to promote cognitive decline as in Alzheimer's disease (AD). A machine learning approach was applied to analyze the impact of various compounds, drawn from the blood of AD patients, including VD and folic acid levels, on the Mini-Mental State Exam (MMSE) in a cohort of 108 patients with AD. The first analysis was aimed at predicting the MMSE at recruitment, whereas a second investigation sought to predict the MMSE after a 4 year follow-up. The simultaneous presence of low levels of VD and folic acid allow to predict MMSE, suggestive of poorer cognitive function. Such results suggest that the low levels of VD and folic acid could be associated with more severe cases of cognitive impairment in AD. It could be hypothesized that simultaneous supplementation of VD and folic acid could slow down the progression of cerebral degeneration at least in a subset of AD individuals.
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Affiliation(s)
- Giuseppe Murdaca
- Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy; (G.M.); (S.B.); (A.N.); (F.M.)
- Ospedale Policlinico San Martino IRCCS, 16132 Genoa, Italy
| | - Sara Banchero
- Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy; (G.M.); (S.B.); (A.N.); (F.M.)
- Ospedale Policlinico San Martino IRCCS, 16132 Genoa, Italy
| | - Alessandro Tonacci
- Clinical Physiology Institute, National Research Council of Italy (IFC-CNR), 56124 Pisa, Italy
| | - Alessio Nencioni
- Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy; (G.M.); (S.B.); (A.N.); (F.M.)
- Ospedale Policlinico San Martino IRCCS, 16132 Genoa, Italy
| | - Fiammetta Monacelli
- Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy; (G.M.); (S.B.); (A.N.); (F.M.)
- Ospedale Policlinico San Martino IRCCS, 16132 Genoa, Italy
| | - Sebastiano Gangemi
- School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy;
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Abstract
It has been 20 years since we first proposed vitamin D as a "possible" neurosteroid.( 1 ) Our work over the last two decades, particularly results from our cellular and animal models, has confirmed the numerous ways in which vitamin D differentiates the developing brain. As a result, vitamin D can now confidently take its place among all other steroids known to regulate brain development.( 2 ) Others have concentrated on the possible neuroprotective functions of vitamin D in adult brains. Here these data are integrated, and possible mechanisms outlined for the various roles vitamin D appears to play in both developing and mature brains and how such actions shape behavior. There is now also good evidence linking gestational and/or neonatal vitamin D deficiency with an increased risk of neurodevelopmental disorders, such as schizophrenia and autism, and adult vitamin D deficiency with certain degenerative conditions. In this mini-review, the focus is on what we have learned over these past 20 years regarding the genomic and nongenomic actions of vitamin D in shaping brain development, neurophysiology, and behavior in animal models. © 2020 The Author. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Darryl Walter Eyles
- Queensland Centre for Mental Health ResearchThe Park Centre for Mental HealthWacolAustralia
- Queensland Brain InstituteUniversity of QueenslandSt. LuciaQueenslandAustralia
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Saleh LA, Almutairi FM, Alorabi WK, Alkuhayli BA, Alzaidi SS, Alzahrani SB, Aljumayi FA, Abduljabbar MH, Alharthi AS, Alsufyani MA, Alhazmi MH, Althobaiti AA, Almutairi FN, Alshehri FS, Altowairqi E, Althobaiti YS. Short- and Long-Term Effects of Vitamin D Treatment on Bacillus Calmette-Guerin-Induced Depressive-Like Behavior in Mice. Neuropsychiatr Dis Treat 2021; 17:711-720. [PMID: 33688194 PMCID: PMC7936677 DOI: 10.2147/ndt.s291793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 02/06/2021] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Depression is one of the most common psychological disorders. The nutritional etiology of the depression proposes that vitamin D may play a significant role in the pathogenesis of depression. Further, vitamin D deficiency has been found to aggravate depression in animals. Therefore, vitamin D treatment might be a potential therapeutic aid in depression management. This study aimed to explore the antidepressant effects of vitamin D in a Bacillus Calmette-Guerin (BCG)-induced depression model. METHODS Thirty-six mice were randomly assigned to short-term and long-term experimental groups. In each group, mice were randomly subcategorized into three subgroups: 1. control (received vehicle), 2. BCG (received BCG [107 CFU/mouse]), and 3. BCG + vitamin D (received vitamin D [60.000 IU/kg] before BCG [107 CFU/mouse] inoculation). After completion of the two experimental periods (3 days for the short-term group and 2 weeks for the long-term group), the mice underwent three behavioral tests: locomotor activity, the forced swimming test (FST), and the tail suspension test (TST). RESULTS Locomotor activity did not significantly differ among the subgroups in either the long-term or short-term groups. In the short-term group, the total immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. However, in the TST, no significant difference was found between the vitamin D-treated group and the BCG group. In the long-term group, the immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. Similarly, the total immobility time on the TST was also significantly lower in the vitamin D-treated mice than in the BCG-treated mice. CONCLUSION Vitamin D is useful in the management of depressive behavior. The potential role of vitamin D in the etiology of depression should be investigated in future work.
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Affiliation(s)
- Lobna A Saleh
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia.,Addiction and Neuroscience Research Unit, College of Pharmacy, Taif University, Taif, Saudi Arabia.,Department of Clinical Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Farooq M Almutairi
- Addiction and Neuroscience Research Unit, College of Pharmacy, Taif University, Taif, Saudi Arabia.,Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, University of Hafar Al-Batin, Hafar Al-Batin, Saudi Arabia
| | - Wejdan K Alorabi
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Bashayr A Alkuhayli
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Shaden S Alzaidi
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Shahad B Alzahrani
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Futun A Aljumayi
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Maram H Abduljabbar
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Ayidh S Alharthi
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Mashhour A Alsufyani
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Mohammed H Alhazmi
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Abdulbari A Althobaiti
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Fahad N Almutairi
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Fahad S Alshehri
- Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ebtehal Altowairqi
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia
| | - Yusuf S Althobaiti
- Department of Pharmacology and Toxicology, College of Pharmacy, Taif University, Taif, 21944, Saudi Arabia.,Addiction and Neuroscience Research Unit, College of Pharmacy, Taif University, Taif, Saudi Arabia.,General Administration for Precursors and Laboratories, General Directorate of Narcotics Control, Ministry of Interior, Riyadh, Saudi Arabia
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Lv L, Tan X, Peng X, Bai R, Xiao Q, Zou T, Tan J, Zhang H, Wang C. The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease. Transl Neurodegener 2020; 9:34. [PMID: 32867847 PMCID: PMC7460797 DOI: 10.1186/s40035-020-00213-2] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 08/06/2020] [Indexed: 12/13/2022] Open
Abstract
In recent years, many studies have investigated the correlations between Parkinson's disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher vitamin D concentrations are linked to better cognitive function and mood in PD patients. Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent, but the FokI (C/T) polymorphism is significantly linked with PD. The occurrence of FokI (C/T) gene polymorphism may influence the risk, severity, and cognitive ability of PD patients, while also possibly influencing the effect of Vitamin D3 supplementation in PD patients. In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission, interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.
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Affiliation(s)
- Lingling Lv
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Xuling Tan
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Xinke Peng
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Rongrong Bai
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Qile Xiao
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Ting Zou
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Jieqiong Tan
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, 410078, China
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, 410078, China
| | - Hainan Zhang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Chunyu Wang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
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36
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Jeong H, Vacanti NM. Systemic vitamin intake impacting tissue proteomes. Nutr Metab (Lond) 2020; 17:73. [PMID: 32863845 PMCID: PMC7449053 DOI: 10.1186/s12986-020-00491-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 08/07/2020] [Indexed: 12/12/2022] Open
Abstract
The kinetics and localization of the reactions of metabolism are coordinated by the enzymes that catalyze them. These enzymes are controlled via a myriad of mechanisms including inhibition/activation by metabolites, compartmentalization, thermodynamics, and nutrient sensing-based transcriptional or post-translational regulation; all of which are influenced as a network by the activities of metabolic enzymes and have downstream potential to exert direct or indirect control over protein abundances. Considering many of these enzymes are active only when one or more vitamin cofactors are present; the availability of vitamin cofactors likely yields a systems-influence over tissue proteomes. Furthermore, vitamins may influence protein abundances as nuclear receptor agonists, antioxidants, substrates for post-translational modifications, molecular signal transducers, and regulators of electrolyte homeostasis. Herein, studies of vitamin intake are explored for their contribution to unraveling vitamin influence over protein expression. As a body of work, these studies establish vitamin intake as a regulator of protein abundance; with the most powerful demonstrations reporting regulation of proteins directly related to the vitamin of interest. However, as a whole, the field has not kept pace with advances in proteomic platforms and analytical methodologies, and has not moved to validate mechanisms of regulation or potential for clinical application.
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Affiliation(s)
- Heesoo Jeong
- Division of Nutritional Sciences, Cornell University, Ithaca, NY USA
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37
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Steardo L, Luciano M, Sampogna G, Carbone EA, Caivano V, Di Cerbo A, Giallonardo V, Palummo C, Vece A, Del Vecchio V, De Fazio P, Fiorillo A. Clinical Severity and Calcium Metabolism in Patients with Bipolar Disorder. Brain Sci 2020; 10:brainsci10070417. [PMID: 32630307 PMCID: PMC7408522 DOI: 10.3390/brainsci10070417] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 06/26/2020] [Accepted: 06/29/2020] [Indexed: 02/07/2023] Open
Abstract
Parathyroid hormone (PTH), vitamin D and serum calcium play a key role in several physiological and pathological conditions. Vitamin D and PTH receptors are largely expressed in the central nervous system and are involved in the modulation of inflammatory responses. Few studies investigated the association between calcium homeostasis imbalance and psychiatric disorders. This study aims to assess calcium homeostasis imbalance in patients with bipolar disorder (BD) and its impact on clinical outcome. We recruited 199 patients with BD, who were administered with validated assessment instruments to investigate depressive, manic and anxiety symptoms, affective temperaments, childhood trauma and global functioning. Serum calcium, vitamin D and PTH levels were assessed in all patients. Levels of PTH correlated with several clinical characteristics, including the diagnosis of bipolar disorder type I (BD-I), the presence of psychotic symptoms, lithium treatment, suicidality, total number of acute episodes and of hospitalizations (p < 0.0001) and seasonality (p < 0.05). At the regression analyses, higher levels of PTH were predicted by early age at onset, number of hospitalizations, aggressive behaviors (p < 0.05), higher Childhood Trauma Questionnaire total score (CTQ) (p < 0.001) and treatment with lithium (p = 0.01). Our findings suggest that the calcium homeostasis could play a role in BD patients, and that PTH levels are correlated with the clinical severity of the disorder.
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Affiliation(s)
- Luca Steardo
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
- Psychiatric Unit, Department of Health Sciences, University Magna Graecia, 88100 Catanzaro, Italy; (E.A.C.); (P.D.F.)
- Correspondence: ; Tel.: +39-0961712801 or +39-3208612071
| | - Mario Luciano
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Gaia Sampogna
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Elvira Anna Carbone
- Psychiatric Unit, Department of Health Sciences, University Magna Graecia, 88100 Catanzaro, Italy; (E.A.C.); (P.D.F.)
| | - Vito Caivano
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Arcangelo Di Cerbo
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Vincenzo Giallonardo
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Carmela Palummo
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Alfonso Vece
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Valeria Del Vecchio
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
| | - Pasquale De Fazio
- Psychiatric Unit, Department of Health Sciences, University Magna Graecia, 88100 Catanzaro, Italy; (E.A.C.); (P.D.F.)
| | - Andrea Fiorillo
- Department of Psychiatry, University of Campania “Luigi Vanvitelli”, 80131 Naples, Italy; (M.L.); (G.S.); (V.C.); (A.D.C.); (V.G.); (C.P.); (A.V.); (V.D.V.); (A.F.)
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Morello M, Pieri M, Zenobi R, Talamo A, Stephan D, Landel V, Féron F, Millet P. The Influence of Vitamin D on Neurodegeneration and Neurological Disorders: A Rationale for its Physio-pathological Actions. Curr Pharm Des 2020; 26:2475-2491. [PMID: 32175837 DOI: 10.2174/1381612826666200316145725] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/11/2020] [Indexed: 12/12/2022]
Abstract
Vitamin D is a steroid hormone implicated in the regulation of neuronal integrity and many brain functions. Its influence, as a nutrient and a hormone, on the physiopathology of the most common neurodegenerative diseases is continuously emphasized by new studies. This review addresses what is currently known about the action of vitamin D on the nervous system and neurodegenerative diseases such as Multiple Sclerosis, Alzheimer's disease, Parkinson's disease and Amyotrophic Lateral Sclerosis. Further vitamin D research is necessary to understand how the action of this "neuroactive" steroid can help to optimize the prevention and treatment of several neurological diseases.
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Affiliation(s)
- Maria Morello
- Clinical Biochemistry, Department of Experimental Medicine, Faculty of Medicine, University of Rome "Tor Vergata" and University Hospital of Tor Vergata, 00133 Rome, Italy
| | - Massimo Pieri
- Clinical Biochemistry, Department of Experimental Medicine, Faculty of Medicine, University of Rome "Tor Vergata" and University Hospital of Tor Vergata, 00133 Rome, Italy
| | - Rossella Zenobi
- Clinical Biochemistry, Department of Experimental Medicine, Faculty of Medicine, University of Rome "Tor Vergata" and University Hospital of Tor Vergata, 00133 Rome, Italy
| | - Alessandra Talamo
- Psychiatric Clinic, University Hospital of Tor Vergata, 00133 Rome, Italy
| | - Delphine Stephan
- Aix Marseille University, CNRS, INP, UMR 7051, Marseille, France
| | - Verena Landel
- Aix Marseille University, CNRS, INP, UMR 7051, Marseille, France
| | - François Féron
- Aix Marseille University, CNRS, INP, UMR 7051, Marseille, France
| | - Pascal Millet
- Aix Marseille University, CNRS, INP, UMR 7051, Marseille, France.,Association UNIVI (Agirc-Arrco), 75010 Paris, France.,Hôpital Gériatrique les Magnolias, Ballainvilliers, France
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39
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Hypovitaminosis D and Aging: Is There a Role in Muscle and Brain Health? Nutrients 2020; 12:nu12030628. [PMID: 32121008 PMCID: PMC7146116 DOI: 10.3390/nu12030628] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Revised: 02/19/2020] [Accepted: 02/21/2020] [Indexed: 02/06/2023] Open
Abstract
The older-adult population is constantly increasing, hence aging and mechanisms leading to aging are a topic raising increasing interest. Hypovitaminosis D is common amongst old patients and has been proposed as causative of several chronic diseases. Here we review the role of hypovitaminosis D and vitamin D supplementation in sarcopenia and dementia, from bench to bedside.
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40
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Egorova O, Myte R, Schneede J, Hägglöf B, Bölte S, Domellöf E, Ivars A'roch B, Elgh F, Ueland PM, Silfverdal SA. Maternal blood folate status during early pregnancy and occurrence of autism spectrum disorder in offspring: a study of 62 serum biomarkers. Mol Autism 2020; 11:7. [PMID: 32131900 PMCID: PMC6964211 DOI: 10.1186/s13229-020-0315-z] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 01/02/2020] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Autism spectrum disorder (ASD) evolves from an interplay between genetic and environmental factors during prenatal development. Since identifying maternal biomarkers associated with ASD risk in offspring during early pregnancy might result in new strategies for intervention, we investigated maternal metabolic biomarkers in relation to occurrence of ASD in offspring using both univariate logistic regression and multivariate network analysis. METHODS Serum samples from 100 women with an offspring diagnosed with ASD and 100 matched control women with typically developing offspring were collected at week 14 of pregnancy. Concentrations of 62 metabolic biomarkers were determined, including amino acids, vitamins (A, B, D, E, and K), and biomarkers related to folate (vitamin B9) metabolism, lifestyle factors, as well as C-reactive protein (CRP), the kynurenine-tryptophan ratio (KTR), and neopterin as markers of inflammation and immune activation. RESULTS We found weak evidence for a positive association between higher maternal serum concentrations of folate and increased occurrence of ASD (OR per 1 SD increase: 1.70, 95% CI 1.22-2.37, FDR adjusted P = 0.07). Multivariate network analysis confirmed expected internal biochemical relations between the biomarkers. Neither inflammation markers nor vitamin D3 levels, all hypothesized to be involved in ASD etiology, displayed associations with ASD occurrence in the offspring. CONCLUSIONS Our findings suggest that high maternal serum folate status during early pregnancy may be associated with the occurrence of ASD in offspring. No inference about physiological mechanisms behind this observation can be made at the present time because blood folate levels may have complex relations with nutritional intake, the cellular folate status and status of other B-vitamins. Therefore, further investigations, which may clarify the potential role and mechanisms of maternal blood folate status in ASD risk and the interplay with other potential risk factors, in larger materials are warranted.
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Affiliation(s)
- Olga Egorova
- Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
| | - Robin Myte
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Jörn Schneede
- Department of Clinical Pharmacology, Pharmacology and Clinical Neurosciences, Umeå University, Umeå, Sweden
| | - Bruno Hägglöf
- Department of Child and Adolescent Psychiatry, Umea University, Umeå, Sweden
| | - Sven Bölte
- Center of Neurodevelopmental Disorders (KIND), Centre for Psychiatry Research, Stockholm, Sweden.,Department of Women's and Children's Health, Karolinska Institutet & Child and Adolescent Psychiatry, Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.,Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, WA, Australia
| | - Erik Domellöf
- Department of Psychology, Umeå University, Umeå, Sweden
| | - Barbro Ivars A'roch
- Department of Child and Adolescent Psychiatry, Umea University, Umeå, Sweden
| | - Fredrik Elgh
- Department of Clinical Microbiology, Umeå University, Umeå, Sweden
| | - Per Magne Ueland
- Bevital AS, Department of Clinical Science, University of Bergen, Bergen, Norway.,Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
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41
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Alzghoul L. Role of Vitamin D in Autism Spectrum Disorder. Curr Pharm Des 2020; 25:4357-4367. [DOI: 10.2174/1381612825666191122092215] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 11/15/2019] [Indexed: 12/19/2022]
Abstract
:
Autism spectrum disorder (ASD) is a pervasive developmental disorder with heterogeneous etiology.
Vitamin D can function as a fat-soluble vitamin as well as a hormone, and can exert its effect through both genomic
and non-genomic mechanisms. In the last decades, several studies have examined the relationship between
vitamin D levels and ASD. These studies demonstrated that low vitamin D status in early development has been
hypothesized as an environmental risk factor for ASD. Both in vivo and in vitro studies have demonstrated that
vitamin D deficiency in early life can alter brain development, dysregulates neurotransmitter balance in the brain,
decreases body and brain antioxidant ability, and alters the immune system in ways that resemble pathological
features commonly seen in ASD. In this review, we focused on the association between vitamin D and ASD. In
addition, the above-mentioned mechanisms of action that link vitamin D deficiency with ASD were also discussed.
Finally, clinical trials of vitamin D supplementation treatment of ASD have also been discussed.
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Affiliation(s)
- Loai Alzghoul
- Department of Physiology and Biochemistry, School of Medicine, The University of Jordan, Amman, Jordan
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Tous M, Villalobos M, Iglesias-Vázquez L, Fernández-Barrés S, Arija V. Vitamin D status during pregnancy and offspring outcomes: a systematic review and meta-analysis of observational studies. Eur J Clin Nutr 2020; 74:36-53. [PMID: 30683894 DOI: 10.1038/s41430-018-0373-x] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 11/09/2018] [Accepted: 11/26/2018] [Indexed: 01/08/2023]
Abstract
BACKGROUND/OBJECTIVES Vitamin D deficiency during pregnancy may influence adverse outcomes in offspring. The aim of this systematic review and meta-analysis of observational studies was to assess the association between low prenatal concentrations of 25(OH)D (by using three different cut-off levels), preterm birth (PTB) and anthropometric and neurodevelopmental outcomes in offspring. SUBJECTS/METHODS Studies reporting data on the association between maternal vitamin D concentrations and offspring outcomes identified through a systematic review of scientific literature published in PubMed/MEDLINE, Scopus and the Cochrane Library databases up to April 2017. RESULTS We included 54 eligible studies. Vitamin D-deficient mothers (<30 nmol/L) had offspring with lower birthweight (MD -87.82 g; 95% CI -119.73, -55.91 g), head circumference (MD -0.19 cm; 95% CI -0.32, -0.06 cm) and a higher risk of small for gestational age (SGA) infants and PTB (OR 1.59; 95% CI 1.24, 2.03) compared to mothers with concentrations ≥30 nmol/L. Vitamin D insufficiency (<50 nmol/L) was associated with a higher risk of SGA and PTB (OR 1.43; 95% CI 1.08, 1.91 and OR 1.28; 95% CI 1.08, 1.52, respectively). Concentrations of 25(OH)D ≥75 nmol/L were not found to be associated with birthweight, SGA or PTB. Offspring of vitamin D-insufficient mothers had lower scores in mental (MD -1.12 points; 95% CI -1.82, -0.42 cm) and language developmental tests (MD -0.35 points; 95% CI -1.00, 0.31 cm). CONCLUSION Maternal vitamin D deficiency is associated with offspring adverse anthropometric outcomes and PTB; insufficiency with a higher risk of SGA, PTB and adverse neurodevelopmental outcomes.
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Affiliation(s)
- Monica Tous
- Research Group in Nutrition and Mental Health (NUTRISAM), Nutrition and Public Health Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain
| | - Marcela Villalobos
- Research Group in Nutrition and Mental Health (NUTRISAM), Nutrition and Public Health Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain
| | - Lucia Iglesias-Vázquez
- Research Group in Nutrition and Mental Health (NUTRISAM), Nutrition and Public Health Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain
| | - Sílvia Fernández-Barrés
- Research Group in Nutrition and Mental Health (NUTRISAM), Nutrition and Public Health Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain
- ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
| | - Victoria Arija
- Research Group in Nutrition and Mental Health (NUTRISAM), Nutrition and Public Health Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, Reus, Spain.
- Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Spain.
- Unitat de Suport a la Recerca Tarragona-Reus, Institut Universitari d'Investigació en Atenció Primària Jordi Gol, Tarragona, Spain.
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Bivona G, Lo Sasso B, Iacolino G, Gambino CM, Scazzone C, Agnello L, Ciaccio M. Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer's disease and Parkinson's disease. Clin Chim Acta 2019; 497:82-87. [PMID: 31330127 DOI: 10.1016/j.cca.2019.07.022] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 07/17/2019] [Accepted: 07/18/2019] [Indexed: 12/16/2022]
Abstract
The current review provides an overview on the development of 25(OH)D measurement standardization tools over the last three decades and clarifies whether there is a role as a serum biomarker for vitamin D in neurological diseases. In the past, a lack of internationally recognized 25(OH)D reference measurement procedures and reference standard materials led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. The vitamin D Standardization Program (VDSP) has been introduced in 2010 to address this problem, however, vitamin D External Quality Assessment Scheme (DEQAS) reports still show substantial sample- to- sample variability. Further, immunoassays, which are mainly used in clinical care laboratories, display analytical issues, including matrix-effects interferences, which cannot be overcome by the standardization process. Hence, liquid chromatography-tandem mass spectrometry (LC/MS-MS) methods should be used to measure 25(OH)D. Low vitamin D serum levels have been found in patients affected by Alzheimer's disease and Parkinson's disease, suggesting a role for vitamin D as a serum biomarker in these diseases. However, few studies reported 25(OH)D standardized results, thus, no clear evidence on the potential role of 25(OH)D serum levels in these diseases exists.
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Affiliation(s)
- Giulia Bivona
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy
| | - Bruna Lo Sasso
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy
| | - Giorgia Iacolino
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy
| | - Caterina Maria Gambino
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy
| | - Concetta Scazzone
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy
| | - Luisa Agnello
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy
| | - Marcello Ciaccio
- Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy; Department of Laboratory Medicine, University-Hospital, Via del Vespro 129, 90141 Palermo, Italy.
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Bivona G, Gambino CM, Iacolino G, Ciaccio M. Vitamin D and the nervous system. Neurol Res 2019; 41:827-835. [PMID: 31142227 DOI: 10.1080/01616412.2019.1622872] [Citation(s) in RCA: 99] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 05/19/2019] [Indexed: 12/19/2022]
Abstract
Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.
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Affiliation(s)
- Giulia Bivona
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
| | - Caterina Maria Gambino
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
| | - Giorgia Iacolino
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
| | - Marcello Ciaccio
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
- Department and U.O.C. Laboratory Medicine, University Hospital "Paolo Giaccone" of Palermo , Palermo , Italy
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Bivona G, Agnello L, Bellia C, Iacolino G, Scazzone C, Lo Sasso B, Ciaccio M. Non-Skeletal Activities of Vitamin D: From Physiology to Brain Pathology. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:341. [PMID: 31284484 PMCID: PMC6680897 DOI: 10.3390/medicina55070341] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 06/27/2019] [Accepted: 07/02/2019] [Indexed: 12/17/2022]
Abstract
Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer's disease (AD) and Parkinson's disease (PD). Indeed, the lack of internationally recognized 25(OH)D3 reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D3 results among research and clinical care laboratories. Thus, most of the literature studies reported unstandardized data, which are of little use and make it difficult to draw conclusions of the role of vitamin D in AD and PD. This review summarizes the extra-skeletal actions of vitamin D, focusing its role in immunomodulation and brain function, and reports the issue of lacking standardized literature data concerning the usefulness of vitamin D as a biomarker in AD and PD.
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Affiliation(s)
- Giulia Bivona
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Luisa Agnello
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Chiara Bellia
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Giorgia Iacolino
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Concetta Scazzone
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Bruna Lo Sasso
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Marcello Ciaccio
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy.
- Department and U.O.C. Laboratory Medicine, University Hospital "Paolo Giaccone" of Palermo, 90127 Palermo, Italy.
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Vitamin D in Synaptic Plasticity, Cognitive Function, and Neuropsychiatric Illness. Trends Neurosci 2019; 42:293-306. [PMID: 30795846 DOI: 10.1016/j.tins.2019.01.003] [Citation(s) in RCA: 99] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 01/25/2019] [Accepted: 01/27/2019] [Indexed: 12/14/2022]
Abstract
Over a billion people worldwide are affected by vitamin D deficiency. Although vitamin D deficiency is associated with impaired cognition, the mechanisms mediating this link are poorly understood. The extracellular matrix (ECM) has now emerged as an important participant of synaptic plasticity and a new hypothesis is that vitamin D may interact with aggregates of the ECM, perineuronal nets (PNNs), to regulate brain plasticity. Dysregulation of PNNs caused by vitamin D deficiency may contribute to the presentation of cognitive deficits. Understanding the molecular mechanisms underpinning the role of vitamin D in brain plasticity and cognition could help identify ways to treat cognitive symptoms in schizophrenia and other neuropsychiatric conditions.
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Jeon SG, Cha MY, Kim JI, Hwang TW, Kim KA, Kim TH, Song KC, Kim JJ, Moon M. Vitamin D-binding protein-loaded PLGA nanoparticles suppress Alzheimer's disease-related pathology in 5XFAD mice. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2019; 17:297-307. [PMID: 30794963 DOI: 10.1016/j.nano.2019.02.004] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Revised: 01/23/2019] [Accepted: 02/07/2019] [Indexed: 10/27/2022]
Abstract
The aggregation and accumulation of amyloid beta (Aβ) peptide is believed to be the primary cause of Alzheimer's disease (AD) pathogenesis. Vitamin D-binding protein (DBP) can attenuate Aβ aggregation and accumulation. A biocompatible polymer poly (D,L-lactic acid-co-glycolic acid) (PLGA) can be loaded with therapeutic agents and control the rate of their release. In the present study, a PLGA-based drug delivery system was used to examine the therapeutic effects of DBP-PLGA nanoparticles in Aβ-overexpressing (5XFAD) mice. DBP was loaded into PLGA nanoparticles and the characteristics of the DBP-PLGA nanoparticles were analyzed. Using a thioflavin-T assay, we observed that DBP-PLGA nanoparticles significantly inhibited Aβ aggregation in vitro. In addition, we found that intravenous injection of DBP-PLGA nanoparticles significantly attenuated the Aβ accumulation, neuroinflammation, neuronal loss and cognitive dysfunction in the 5XFAD mice. Collectively, our results suggest that DBP-PLGA nanoparticles could be a promising therapeutic candidate for the treatment of AD.
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Affiliation(s)
- Seong Gak Jeon
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Moon-Yong Cha
- Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
| | - Jin-Il Kim
- Department of Nursing, College of Nursing, Jeju National University, Jeju-si, Republic of Korea
| | - Tae Woong Hwang
- Department of Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
| | - Kyoung Ah Kim
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea
| | - Tae Hyoung Kim
- Department of Biomedical Materials, Konyang University, Daejeon, Republic of Korea
| | - Ki Chang Song
- Department of Biomedical Materials, Konyang University, Daejeon, Republic of Korea
| | - Jwa-Jin Kim
- Department of Biomedical Science, Jungwon University, Goesan-gun, Chungbuk, Republic of Korea; Department of Nephrology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
| | - Minho Moon
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea.
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Moretti R, Morelli ME, Caruso P. Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact. Int J Mol Sci 2018; 19:2245. [PMID: 30065237 PMCID: PMC6121649 DOI: 10.3390/ijms19082245] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 07/25/2018] [Accepted: 07/26/2018] [Indexed: 12/22/2022] Open
Abstract
It is widely known that vitamin D receptors have been found in neurons and glial cells, and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. Vitamin D helps the regulation of neurotrophin, neural differentiation, and maturation, through the control operation of growing factors synthesis (i.e., neural growth factor [NGF] and glial cell line-derived growth factor (GDNF), the trafficking of the septohippocampal pathway, and the control of the synthesis process of different neuromodulators (such as acetylcholine [Ach], dopamine [DA], and gamma-aminobutyric [GABA]). Based on these assumptions, we have written this review to summarize the potential role of vitamin D in neurological pathologies. This work could be titanic and the results might have been very fuzzy and even incoherent had we not conjectured to taper our first intentions and devoted our interests towards three mainstreams, demyelinating pathologies, vascular syndromes, and neurodegeneration. As a result of the lack of useful therapeutic options, apart from the disease-modifying strategies, the role of different risk factors should be investigated in neurology, as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long-term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.
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Affiliation(s)
- Rita Moretti
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
| | - Maria Elisa Morelli
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
| | - Paola Caruso
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
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Wang Q, Zhu Z, Liu Y, Tu X, He J. Relationship between serum vitamin D levels and inflammatory markers in acute stroke patients. Brain Behav 2018; 8:e00885. [PMID: 29484258 PMCID: PMC5822590 DOI: 10.1002/brb3.885] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 10/13/2017] [Accepted: 11/01/2017] [Indexed: 02/06/2023] Open
Abstract
Introduction Low serum vitamin D levels are associated with the development of poststroke depression (PSD). Inflammatory markers play an important role in pathophysiology of PSD. The relationship between vitamin D levels and inflammatory markers has been discussed in nonstroke individuals. The purposes of this study were to explore the relationship between vitamin D levels and inflammatory markers in acute stroke patients and examine the effect of vitamin D and inflammatory markers on PSD. Methods A total of 152 acute stroke patients were recruited. Serum levels of 25-hydroxyvitamin D and inflammatory markers were measured by standardized laboratory methods. Depression symptoms were assessed with the 17-item Hamilton Depression Scale (HAMD-17). Patients with the HAMD-17 scores ≥7 were identified to have depression symptoms. Results Serum vitamin D levels were negatively correlated with serum levels of interleukin-6 and high-sensitivity C-reactive protein (hsCRP) (r = -.244, p = .002; r = -.231, p = .004). Multiple regression analysis showed that interleukin-6 and hsCRP levels were associated with vitamin D levels (B = -0.355, p = .003; B = -2.085, p = .006), whereas age, height, weight, leukocyte count, neutrophil ratio, and lymphocyte rate could be omitted without changing the results. In multivariate analyses, the serum levels of vitamin D and interleukin-6 were associated with the development of PSD after adjusted possible variables (OR = 0.976, 95% CI: 0.958-0.994, p = .009; OR = 1.029, 95% CI: 1.003-1.055, p = .027). Conclusions Serum vitamin D levels are inversely associated with the levels of interleukin-6 and hsCRP, suggesting a potential anti-inflammatory role for vitamin D in stroke individuals.
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Affiliation(s)
- Qiongzhang Wang
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Zhuoying Zhu
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Yuntao Liu
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Xinjie Tu
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Jincai He
- Department of NeurologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
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Lerner PP, Sharony L, Miodownik C. Association between mental disorders, cognitive disturbances and vitamin D serum level: Current state. Clin Nutr ESPEN 2018; 23:89-102. [DOI: 10.1016/j.clnesp.2017.11.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2016] [Revised: 07/31/2017] [Accepted: 11/29/2017] [Indexed: 01/02/2023]
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