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Tang G, Guo Y, Li R, Wang Y, Yang J, Gao S, Liu J. Lateral habenula 5-HT 1B receptors are involved in regulation of anxiety-like behaviors in parkinsonian rats. Neurochem Int 2024; 177:105766. [PMID: 38750961 DOI: 10.1016/j.neuint.2024.105766] [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: 03/25/2024] [Revised: 05/04/2024] [Accepted: 05/12/2024] [Indexed: 06/04/2024]
Abstract
Although the output of the lateral habenula (LHb) controls the activity of midbrain dopaminergic and serotonergic systems, which are implicated in the pathophysiology of anxiety, it is not clear the role of LHb 5-HT1B receptors in regulation of anxiety-like behaviors, particularly in Parkinson's disease-related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, led to decreased normalized δ power and increased normalized θ power in the LHb, and decreased dopamine (DA) level in the prelimbic cortex (PrL) compared with sham rats. Down-regulation of LHb 5-HT1B receptors by RNA interference produced anxiety-like effects, decreased normalized δ power and increased normalized θ power in the LHb in both sham and lesioned rats. Further, intra-LHb injection of 5-HT1B receptor agonist CP93129 induced anxiolytic-like responses, increased normalized δ power and decreased normalized θ power in the LHb, and increased DA and serotonin (5-HT) release in the PrL; conversely, 5-HT1B receptor antagonist SB216641 produced anxiety-like effects, decreased normalized δ power and increased normalized θ power in the LHb, and decreased DA and 5-HT release in the PrL in sham and lesioned rats. Additionally, effects of CP93129 and SB216641 on the behaviors, normalized δ and θ power in the LHb, and DA and 5-HT release in the PrL were decreased in lesioned rats, which were consistent with down-regulation of LHb 5-HT1B receptors after DA depletion. Collectively, these findings suggest that 5-HT1B receptors in the LHb are involved in the regulation of anxiety-like behaviors.
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Affiliation(s)
- Guoyi Tang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Yuan Guo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Ruotong Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Yixuan Wang
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Jie Yang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Shasha Gao
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
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Yim J, Hwang YS, Lee JJ, Kim JH, Baek JY, Jeong J, Choi YI, Jin BK, Park SB. Inflachromene ameliorates Parkinson's disease by targeting Nrf2-binding Keap1. Chem Sci 2024; 15:3588-3595. [PMID: 38455026 PMCID: PMC10915859 DOI: 10.1039/d3sc06997d] [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: 12/30/2023] [Accepted: 01/15/2024] [Indexed: 03/09/2024] Open
Abstract
Parkinson's disease (PD) is the most common neurodegenerative disease characterized by movement disorder. Despite current therapeutic efforts, PD progression and the loss of dopaminergic neurons in the substantia nigra remain challenging to prevent due to the complex and unclear molecular mechanism involved. We adopted a phenotype-based drug screening approach with neuronal cells to overcome these limitations. In this study, we successfully identified a small molecule with a promising therapeutic effect for PD treatment, called inflachromene (ICM), through our phenotypic screening strategy. Subsequent target identification using fluorescence difference in two-dimensional gel electrophoresis (FITGE) revealed that ICM ameliorates PD by targeting a specific form of Keap1. This interaction led to upregulating various antioxidants, including HO-1, NQO1, and glutathione, ultimately alleviating PD symptoms. Furthermore, ICM exhibited remarkable efficacy in inhibiting the loss of dopaminergic neurons and the activation of astrocytes and microglia, which are critical factors in PD pathology. Our findings suggest that the phenotypic approach employed in this study identified that ICM has potential for PD treatment, offering new hope for more effective therapeutic interventions in the future.
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Affiliation(s)
- Junhyeong Yim
- Department of Biophysics and Chemical Biology, Seoul National University Seoul 08826 Korea
| | - Yoon Soo Hwang
- CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University Seoul 08826 Korea
| | | | | | - Jeong Yeob Baek
- Department of Biochemistry & Molecular Biology, School of Medicine, Kyung Hee University Seoul 02447 Korea
| | - Jaeyeong Jeong
- Department of Biochemistry & Molecular Biology, School of Medicine, Kyung Hee University Seoul 02447 Korea
| | | | - Byung Kwan Jin
- Department of Biochemistry & Molecular Biology, School of Medicine, Kyung Hee University Seoul 02447 Korea
| | - Seung Bum Park
- Department of Biophysics and Chemical Biology, Seoul National University Seoul 08826 Korea
- CRI Center for Chemical Proteomics, Department of Chemistry, Seoul National University Seoul 08826 Korea
- SPARK Biopharma, Inc. Seoul 08791 Korea
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Joshi D, Prasad S, Saini J, Ingalhalikar M. Role of Arterial Spin Labeling (ASL) Images in Parkinson's Disease (PD): A Systematic Review. Acad Radiol 2023; 30:1695-1708. [PMID: 36435728 DOI: 10.1016/j.acra.2022.11.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/19/2022] [Accepted: 11/01/2022] [Indexed: 11/24/2022]
Abstract
RATIONALE AND OBJECTIVES Parkinson's disease is a chronic progressive neurodegenerative disorder with standard structural MRIs often showing no gross abnormalities. Quantitative perfusion MRI modality Arterial Spin Labeling (ASL) is helpful in identifying PD specific perfusion patterns. Absolute Cerebral blood flow (CBF) measurement using ASL provides insights into regional perfusion abnormalities. We reviewed the role of ASL to identify specific brain regions responsible for motor, non-motor symptoms and neurovascular changes observed in PD. Challenges in assessing the blood perfusion level are discussed with future development for improving the evaluation of ASL perfusion maps. MATERIALS AND METHODS We included CBF quantification studies using ASL for PD diagnosis. A systematic search was performed in Pubmed, Scopus and Web of Science. The perfusion parameters CBF and arterial arrival time (AAT) measured using ASL were considered for brain region assessment. Clinical aspects of PD have been analyzed using ASL perfusion maps. RESULTS The systematic search identified 153 unique records. Thirty articles were selected after verification of inclusion and exclusion criteria. Voxel and region-based analyses in white and gray matter tissues have been performed to identify PD-specific perfusion patterns by reported articles. Predominant brain regions such as basal ganglia sub-regions, frontoparietal network, precuneus, occipital lobe, sensory motor area regions, visual network, which are associated with motor and non-motor symptoms in PD, were identified with CBF hypoperfusion, indicating neuronal loss and cerebrovascular dysfunction. CONCLUSION CBF and AAT values derived from ASL can potentially be used as biomarkers to discriminate PD from similar brain-related disorders.
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Affiliation(s)
- Dhanashri Joshi
- Symbiosis Center of Medical Image Analysis, Symbiosis International (Deemed) University, Pune,MH, India
| | - Shweta Prasad
- Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, KA, India; Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bengaluru,, KA, India
| | - Jitender Saini
- Department of Neuroimaging & Interventional Radiology, National Institute of Mental Health and Neurosciences, Bengaluru, KA, India
| | - Madhura Ingalhalikar
- Symbiosis Center of Medical Image Analysis, Symbiosis International (Deemed) University, Pune,MH, India.
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Tang GY, Wang RJ, Guo Y, Liu J. 5-HT 1B receptor-AC-PKA signal pathway in the lateral habenula is involved in the regulation of depressive-like behaviors in 6-hydroxydopamine-induced Parkinson's rats. Neurol Res 2023; 45:127-137. [PMID: 36127643 DOI: 10.1080/01616412.2022.2124797] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVE The aim of the present study was to investigate whether serotonin1B (5-HT1B) receptor-adenylate cyclase (AC)-protein kinase A (PKA) signal pathway in the lateral habenula (LHb) is involved in Parkinson's disease-related depression in sham-lesioned and substantia nigra pars compacta (SNc)-lesioned rats. METHODS The sucrose preference and forced swim tests were used to measure depressive-like behaviors. In vivo electrophysiology and microdialysis were performed to observe the firing activity of LHb neurons and GABA and glutamate release in the LHb, respectively. Western blotting was used to analyze protein expression of 5-HT1B receptors, AC and phosphorylated PKA at threonine 197 site (p-PKA-Thr197) in the LHb. RESULTS Unilateral 6-hydroxydopamine lesions of the SNc in rats induced depressive-like behaviors. Intra-LHb injection of 5-HT1B receptor agonist CP93129 produced antidepressant-like effects and the antagonist SB216641 induced depressive-like behaviors in sham-lesioned and SNc-lesioned rats. Further, pretreatment with AC inhibitor SQ22536 and PKA inhibitor KT5720 blocked the behavioral effects of CP93129 in the two groups of rats, respectively. CP93129 decreased the firing rate of LHb neurons and release of GABA and glutamate, but increased the GABA/glutamate ratio, while SB216641 induced the opposite effects. Compared with sham-lesioned rats, effects of CP93129 and SB216641 on the depressive-like behaviors, electrophysiology, and microdialysis were decreased in SNc-lesioned rats, which were associated with decreased expression of 5-HT1B receptors, AC and p-PKA-Thr197 in the LHb. CONCLUSION 5-HT1B receptor-AC-PKA signal pathway in the LHb is involved in the regulation of depressive-like behaviors, and depletion of DA reduces activity of 5-HT1B receptor-AC-PKA signal pathway.
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Affiliation(s)
- Guo Yi Tang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Run Jia Wang
- Department of Clinical Medicine, Xi'an Medical University, Xi'an, China
| | - Yuan Guo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China
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Oh M, Kim JW, Lee SM. Delusional parasitosis as premotor symptom of parkinson’s disease: A case report. World J Clin Cases 2022; 10:2858-2863. [PMID: 35434114 PMCID: PMC8968791 DOI: 10.12998/wjcc.v10.i9.2858] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/16/2021] [Accepted: 01/23/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Delusional parasitosis is characterized by a false belief of being infested with parasites, insects, or worms. This illness is observed in patients with Parkinson’s disease and is usually related to dopaminergic treatment. To our knowledge, no cases of delusional parasitosis have been reported as a premotor symptom or non-motor symptom of Parkinson’s disease.
CASE SUMMARY A 75-year-old woman presented with a complaint of itching that she ascribed to the presence of insects in her skin, and she had erythematous plaques on her trunk, arms, buttocks, and face. These symptoms started two months before the visit to the hospital. She took medication, including antipsychotics, with a diagnosis of delusional parasitosis, and the delusion improved after three months. A year later, antipsychotics were discontinued, and anxiety and depression were controlled with medication. However, she complained of bradykinesia, masked face, hand tremor, and mild rigidity, and we performed fluorinated N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography (PET), which showed mildly decreased DAT binding in the right anterior putamen and caudate nucleus. Parkinson’s disease was diagnosed on the basis of PET and clinical symptoms.
CONCLUSION In conclusion, delusional parasitosis can be considered a non-motor sign of Parkinson’s disease along with depression, anxiety, and constipation.
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Affiliation(s)
- Miae Oh
- Department of Psychiatry, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul 02447, South Korea
| | - Jong Woo Kim
- Department of Psychiatry, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul 02447, South Korea
| | - Sang-Min Lee
- Department of Psychiatry, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul 02447, South Korea
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Arten TL, Hamdan AC. NExecutive functions and memory in Parkinson's disease patients with Deep Brain Stimulation. AGING AND HEALTH RESEARCH 2022. [DOI: 10.1016/j.ahr.2022.100065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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Zaehle T, Galazky I, Krauel K. The LC-NE system as a potential target for neuromodulation to ameliorate non-motor symptoms in Parkinson's disease. Auton Neurosci 2021; 236:102901. [PMID: 34757309 DOI: 10.1016/j.autneu.2021.102901] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 09/06/2021] [Accepted: 10/15/2021] [Indexed: 01/24/2023]
Abstract
Parkinson's disease (PD) is associated with severe motor symptoms but also with several non-motor symptoms (NMS). A substantial reduction of norepinephrine (NE) levels in various brain regions reflecting an extensive loss of innervation from the LC has been assumed as causal for the development of NMS and specifically of attentional impairments in PD. Transcutaneous auricular vagus nerve stimulation (taVNS) is a new, non-invasive neurostimulation method supposed to modulate the LC-NE system in humans. In the current opinion paper, we introduce taVNS as a systemic approach to directly affect NE neurotransmission in healthy as well as clinical populations and discuss its potential as therapeutic option for the treatment of NMS, specifically attentional deficits, in patients with PD. Here, we first describe the LC-NE system and discuss how LC-NE dysfunction might affects cognition in PD before detailing the mode of action of taVNS and proposing its use to modulate cognitive deficits in these patients.
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Affiliation(s)
- Tino Zaehle
- Department of Neurology, Otto-von-Guericke-University, Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg 39106, Germany
| | - Imke Galazky
- Department of Neurology, Otto-von-Guericke-University, Magdeburg, Germany
| | - Kerstin Krauel
- Center for Behavioral Brain Sciences (CBBS), Magdeburg 39106, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany.
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8
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Gopar-Cuevas Y, Duarte-Jurado AP, Diaz-Perez RN, Saucedo-Cardenas O, Loera-Arias MJ, Montes-de-Oca-Luna R, Rodriguez-Rocha H, Garcia-Garcia A. Pursuing Multiple Biomarkers for Early Idiopathic Parkinson's Disease Diagnosis. Mol Neurobiol 2021; 58:5517-5532. [PMID: 34350555 DOI: 10.1007/s12035-021-02500-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Accepted: 07/16/2021] [Indexed: 12/21/2022]
Abstract
Parkinson's disease (PD) ranks first in the world as a neurodegenerative movement disorder and occurs most commonly in an idiopathic form. PD patients may have motor symptoms, non-motor symptoms, including cognitive and behavioral changes, and symptoms related to autonomic nervous system (ANS) failures, such as gastrointestinal, urinary, and cardiovascular symptoms. Unfortunately, the diagnostic accuracy of PD by general neurologists is relatively low. Currently, there is no objective molecular or biochemical test for PD; its diagnosis is based on clinical criteria, mainly by cardinal motor symptoms, which manifest when patients have lost about 60-80% of dopaminergic neurons. Therefore, it is urgent to establish a panel of biomarkers for the early and accurate diagnosis of PD. Once the disease is accurately diagnosed, it may be easier to unravel idiopathic PD's pathogenesis, and ultimately, finding a cure. This review discusses several biomarkers' potential to set a panel for early idiopathic PD diagnosis and future directions.
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Affiliation(s)
- Yareth Gopar-Cuevas
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico
| | - Ana P Duarte-Jurado
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico
| | - Rosa N Diaz-Perez
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico
| | - Odila Saucedo-Cardenas
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico.,Departamento de Genética Molecular, Centro de Investigación Biomédica del Noreste, Delegación Nuevo León, Instituto Mexicano del Seguro Social, Monterrey, Mexico
| | - Maria J Loera-Arias
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico
| | - Roberto Montes-de-Oca-Luna
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico
| | - Humberto Rodriguez-Rocha
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico.
| | - Aracely Garcia-Garcia
- Departamento de Histología, Facultad de Medicina, Universidad Autónoma de Nuevo León, 64460, Monterrey, Mexico.
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Wilt JA, Merner AR, Zeigler J, Montpetite M, Kubu CS. Does Personality Change Follow Deep Brain Stimulation in Parkinson's Disease Patients? Front Psychol 2021; 12:643277. [PMID: 34393883 PMCID: PMC8361492 DOI: 10.3389/fpsyg.2021.643277] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 03/15/2021] [Indexed: 12/19/2022] Open
Abstract
Deep Brain Stimulation (DBS) has emerged as a safe, effective, and appealing treatment for Parkinson's Disease (PD), particularly for improving motor symptoms (e. g., tremor, bradykinesia, and rigidity). However, concerns have been raised about whether DBS causes psychological changes, including changes to personality: characteristic and relatively stable patterns of affect, behavior, cognition, and desire. In this article, after first presenting some background information about PD and DBS, we examined evidence obtained from various empirical research methods (quantitative, qualitative, and mixed methods for evaluating patient valued characteristics) pertaining to whether DBS causes personality change. General limitations across research methods include a lack of randomized clinical trials and small sample sizes. We organized our review of findings according to different layers of personality variables: dispositional traits (including personality pathology), characteristic adaptations, and narrative identity. Though most work has been done on dispositional traits, there is not much evidence that dispositional traits change following DBS. Little work has been done on characteristic adaptations, but there is somewhat consistent evidence for positive perceived progress toward goals across a number of domains: routine activities, work, social/relational, and leisure. Nascent work on narrative identity holds promise for revealing issues around self-image that may be common following DBS. We listed a number of strategies for advancing research, highlighting opportunities related to personality conceptualization, personality assessment, and interdisciplinary scholarship. Finally, we offer practical applications of our findings for the informed consent process and for ongoing treatment.
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Affiliation(s)
- Joshua A Wilt
- Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, United States
| | - Amanda R Merner
- Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, United States.,Department of Neurology, Cleveland Clinic, Cleveland, OH, United States
| | - Jaclyn Zeigler
- Department of Neurology, Cleveland Clinic, Cleveland, OH, United States
| | | | - Cynthia S Kubu
- Department of Neurology, Cleveland Clinic, Cleveland, OH, United States.,Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, United States
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10
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Yang Y, Liu J, Wang Y, Wu X, Li L, Bian G, Li W, Yuan H, Zhang Q. Blockade of pre-synaptic and post-synaptic GABA B receptors in the lateral habenula produces different effects on anxiety-like behaviors in 6-hydroxydopamine hemiparkinsonian rats. Neuropharmacology 2021; 196:108705. [PMID: 34246684 DOI: 10.1016/j.neuropharm.2021.108705] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/28/2021] [Accepted: 07/07/2021] [Indexed: 01/20/2023]
Abstract
Although the output of the lateral habenula (LHb) controls the activity of midbrain dopaminergic and serotonergic systems, which are implicated in the pathophysiology of anxiety, it is not known how blockade of GABAB receptors in the region affects anxiety-like behaviors, particularly in Parkinson's disease-related anxiety. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta in rats induced anxiety-like behaviors, led to hyperactivity of LHb neurons and decreased the level of extracellular dopamine (DA) in the basolateral amygdala (BLA) compared to sham-lesioned rats. Intra-LHb injection of pre-synaptic GABAB receptor antagonist CGP36216 produced anxiolytic-like effects, while the injection of post-synaptic GABAB receptor antagonist CGP35348 induced anxiety-like responses in both groups. Further, intra-LHb injection of CGP36216 decreased the firing rate of the neurons, and increased the GABA/glutamate ratio in the LHb and release of DA and serotonin (5-HT) in the BLA; conversely, CGP35348 increased the firing rate of the neurons and decreased the GABA/glutamate ratio and release of DA and 5-HT in sham-lesioned and the lesioned rats. However, the doses of the antagonists producing these behavioral effects in the lesioned rats were lower than those in sham-lesioned rats, and the duration of action of the antagonists on the firing rate of the neurons and release of the neurotransmitters was prolonged in the lesioned rats. Collectively, these findings suggest that pre-synaptic and post-synaptic GABAB receptors in the LHb are involved in the regulation of anxiety-like behaviors, and degeneration of the nigrostriatal pathway up-regulates function and/or expression of these receptors.
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Affiliation(s)
- Yaxin Yang
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Yixuan Wang
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Xiang Wu
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Libo Li
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Guanyun Bian
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Wenjuan Li
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Haifeng Yuan
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Qiaojun Zhang
- Department of Rehabilitation Medicine, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
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11
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Lyu S, Guo Y, Zhang L, Tang G, Li R, Yang J, Gao S, Li W, Liu J. Downregulation of astroglial glutamate transporter GLT-1 in the lateral habenula is associated with depressive-like behaviors in a rat model of Parkinson's disease. Neuropharmacology 2021; 196:108691. [PMID: 34197892 DOI: 10.1016/j.neuropharm.2021.108691] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 06/06/2021] [Accepted: 06/24/2021] [Indexed: 01/11/2023]
Abstract
Recent studies show that neuron-glial communication plays an important role in neurological diseases. Particularly, dysfunction of astroglial glutamate transporter GLT-1 has been involved in various neuropsychiatric disorders, including Parkinson's disease (PD) and depression. Our previous studies indicated hyperactivity of neurons in the lateral habenula (LHb) of hemiparkinsonian rats with depressive-like behaviors. Thus, we hypothesized that impaired expression or function of GLT-1 in the LHb might be a potential contributor to LHb hyperactivity, which consequently induces PD-related depression. In the study, unilateral lesions of the substantia nigra pars compacta (SNc) by 6-hydroxydopamine in rats induced depressive-like behaviors and resulted in neuronal hyperactivity as well as increased glutamate levels in the LHb compared to sham-lesioned rats. Intra-LHb injection of GLT-1 inhibitor WAY-213613 induced the depressive-like behaviors in both groups, but the dose producing behavioral effects in the lesioned rats was lower than that of sham-lesioned rats. In the two groups of rats, WAY-213613 increased the firing rate of LHb neurons and extracellular levels of glutamate, and these excitatory effects in the lesioned rats lasted longer than those in sham-lesioned rats. The functional changes of the GLT-1 which primarily expresses in astrocytes in the LHb may attribute to its downregulation after degeneration of the nigrostriatal pathway. Bioinformatics analysis showed that GLT-1 is correlated with various biomarkers of PD and depression risks. Collectively, our study suggests that astroglial GLT-1 in the LHb regulates the firing activity of the neurons, whereupon its downregulation and dysfunction are closely associated with PD-related depression.
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Affiliation(s)
- Shuxuan Lyu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Yuan Guo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Li Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Guoyi Tang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Ruotong Li
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Jie Yang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Shasha Gao
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Wenjuan Li
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
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Lyu S, Guo Y, Zhang L, Wang Y, Tang G, Li R, Yang J, Gao S, Ma B, Liu J. Blockade of GABA transporter-1 and GABA transporter-3 in the lateral habenula improves depressive-like behaviors in a rat model of Parkinson's disease. Neuropharmacology 2020; 181:108369. [DOI: 10.1016/j.neuropharm.2020.108369] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 10/15/2020] [Accepted: 10/19/2020] [Indexed: 12/23/2022]
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Hui Y, Du C, Xu T, Zhang Q, Tan H, Liu J. Dopamine D4 receptors in the lateral habenula regulate depression-related behaviors via a pre-synaptic mechanism in experimental Parkinson's disease. Neurochem Int 2020; 140:104844. [DOI: 10.1016/j.neuint.2020.104844] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/19/2020] [Accepted: 08/30/2020] [Indexed: 11/30/2022]
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Measurement of baseline locomotion and other behavioral traits in a common marmoset model of Parkinson's disease established by a single administration regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: providing reference data for efficacious preclinical evaluations. Behav Pharmacol 2020; 31:45-60. [PMID: 31625972 PMCID: PMC6964884 DOI: 10.1097/fbp.0000000000000509] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Supplemental Digital Content is available in the text. Baseline locomotion and behavioral traits in the common marmoset Parkinson's disease model were examined to provide basic information for preclinical evaluations of medical treatments. A single regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine at a cumulative dose of 5 mg/kg as the free base over three consecutive days was administered subcutaneously to 10 marmosets. Data obtained from these marmosets were compared to pre-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine levels or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine free marmosets. After the single regimen, reduced daily locomotion, a measure of immobility (a primary sign of Parkinsonism), was observed for more than a year. A moving tremor was also observed by visual inspection during this period. When apomorphine (0.13 mg/kg, s.c.) was administered, either right or left circling behavior was observed in a cylindrical chamber in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets, suggestive of unequal neural damage between the two brain hemispheres to different extents. MRI revealed that T1 relaxation time in the right substantia nigra correlated with right circling in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets. Histology was supportive of dopaminergic neural loss in the striatum. These results increase our understanding of the utility and limitations of the Parkinson's disease model in marmosets with a single 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine regimen, and provide reference data for efficacious preclinical evaluations.
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Yang S, Wang F, Yang L, Xu F, Luo M, Chen X, Feng X, Zou X. The physical significance of acoustic parameters and its clinical significance of dysarthria in Parkinson's disease. Sci Rep 2020; 10:11776. [PMID: 32678256 PMCID: PMC7366911 DOI: 10.1038/s41598-020-68754-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/23/2020] [Indexed: 11/09/2022] Open
Abstract
Dysarthria is universal in Parkinson's disease (PD) during disease progression; however, the quality of vocalization changes is often ignored. Furthermore, the role of changes in the acoustic parameters of phonation in PD patients remains unclear. We recruited 35 PD patients and 26 healthy controls to perform single, double, and multiple syllable tests. A logistic regression was performed to differentiate between protective and risk factors among the acoustic parameters. The results indicated that the mean f0, max f0, min f0, jitter, duration of speech and median intensity of speaking for the PD patients were significantly different from those of the healthy controls. These results reveal some promising indicators of dysarthric symptoms consisting of acoustic parameters, and they strengthen our understanding about the significance of changes in phonation by PD patients, which may accelerate the discovery of novel PD biomarkers.
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Affiliation(s)
- Shu Yang
- College of Medical Information Engineering, Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan, China
- Department of Public Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Fengbo Wang
- Department of Rehabilitation, First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Liqiong Yang
- Department of Pharmacy, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Fan Xu
- Department of Public Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Man Luo
- Department of Neurology, First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Xiaqing Chen
- Department of Neurology, First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China
| | - Xixi Feng
- Department of Public Health, Chengdu Medical College, Chengdu, 610500, Sichuan, China.
| | - Xianwei Zou
- Department of Neurology, First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, China.
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Patient-Reported and Performance-Based Outcome Measures for Functional Mobility and Activity Limitation in Individuals with Parkinson's Disease. ANADOLU KLINIĞI TIP BILIMLERI DERGISI 2020. [DOI: 10.21673/anadoluklin.622194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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17
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Bian G, Liu J, Guo Y, Yang Y, Li L, Qiao H, Li W, Xu T, Zhang Q. Kv7.2 subunit-containing M-type potassium channels in the lateral habenula are involved in the regulation of working memory in parkinsonian rats. Neuropharmacology 2020; 168:108012. [PMID: 32067988 DOI: 10.1016/j.neuropharm.2020.108012] [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: 12/04/2019] [Revised: 02/06/2020] [Accepted: 02/13/2020] [Indexed: 12/13/2022]
Abstract
Although the lateral habenula (LHb) is involved in the regulation of multiple brain functions and this region expresses abundant M-type potassium channel (M-channel) subunits Kv7.2 and Kv7.3, the role of M-channels in regulating working memory is unclear, particularly in Parkinson's disease (PD). Here we tested the effects of activation and blockade of LHb M-channels on working memory by the T-maze rewarded alternation test in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra compacta (SNc). The SNc lesion induced working memory impairment, increased the firing rate of LHb neurons, decreased dopamine (DA) level in the ventral medial prefrontal cortex (vmPFC) and reduced the expression of Kv7.2 subunit in the LHb. Intra-LHb injection of M-channel activator retigabine induced enhancement of working memory in SNc sham-lesioned and SNc-lesioned rats; conversely, the injection of M-channel blocker XE-991 impaired working memory in the two groups of rats. However, doses producing significant effects in SNc-lesioned rats were higher than those in SNc sham-lesioned rats. Further, intra-LHb injection of retigabine decreased the firing rate of LHb neurons and increased release of DA and serotonin (5-HT) in the vmPFC, while XE-991 increased the firing rate and decreased DA and 5-HT release in the two groups of rats. Compared with SNc sham-lesioned rats, the duration of M-channel activation and blockade action on the firing rate of the neurons and release of DA and 5-HT was significantly shortened in SNc-lesioned rats, which was consistent with reduced expression of Kv7.2 subunit in the LHb after lesioning the SNc. Collectively, these findings suggest involvement of LHb Kv7.2 subunit-containing M-channels in working memory impairment in SNc-lesioned rats, and that enhanced or impaired working memory after activation or blockade of M-channels in the LHb is related to the changes in the firing activity of LHb neurons and DA and 5-HT release in the vmPFC.
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Affiliation(s)
- Guanyun Bian
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Yuan Guo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China
| | - Yaxin Yang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Libo Li
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Hongfei Qiao
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Wenjuan Li
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Tian Xu
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China
| | - Qiaojun Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710004, China.
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Zhang J, Lv S, Tang G, Bian G, Yang Y, Li R, Yang J, Liu J. Activation of calcium-impermeable GluR2-containing AMPA receptors in the lateral habenula produces antidepressant-like effects in a rodent model of Parkinson's disease. Exp Neurol 2019; 322:113058. [DOI: 10.1016/j.expneurol.2019.113058] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Revised: 09/05/2019] [Accepted: 09/05/2019] [Indexed: 12/11/2022]
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Blockade of calcium-permeable AMPA receptors in the lateral habenula produces increased antidepressant-like effects in unilateral 6-hydroxydopamine-lesioned rats compared to sham-lesioned rats. Neuropharmacology 2019; 157:107687. [DOI: 10.1016/j.neuropharm.2019.107687] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2019] [Revised: 06/20/2019] [Accepted: 06/24/2019] [Indexed: 01/28/2023]
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Fan LL, Deng B, Yan JB, Hu ZH, Ren AH, Yang DW. Lesions of mediodorsal thalamic nucleus reverse abnormal firing of the medial prefrontal cortex neurons in parkinsonian rats. Neural Regen Res 2019; 14:1635-1642. [PMID: 31089064 PMCID: PMC6557112 DOI: 10.4103/1673-5374.255982] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease. However, the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear. To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex, a model of Parkinson’s disease was established by injecting 8 µg 6-hydroxydopamine into the substantia nigra compacta of rats. After 1 or 3 weeks, 0.3 µg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain. At 3 or 5 weeks after the initial injury, neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically. The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining. Results demonstrated that after injury, the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats. Compared with normal medial prefrontal cortical neurons, at 3 and 5 weeks after substantia nigra compacta injury, the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge, with an increased discharge interval. The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge, but the discharge interval was only higher at 3 weeks. At 3 weeks after the combined lesions, the discharge frequency, discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex. These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex. The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury. All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University, China (approval No. XJTULAC2017-067) on August 26, 2017.
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Affiliation(s)
- Ling-Ling Fan
- Department of Physiology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China
| | - Bo Deng
- Department of Physiology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China
| | - Jun-Bao Yan
- Department of Physiology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China
| | - Zhi-Hong Hu
- Department of Physiology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China
| | - Ai-Hong Ren
- Department of Physiology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China
| | - Dong-Wei Yang
- Department of Physiology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China
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21
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Kornblith ES, Casey SL, Lobdell DT, Colledge MA, Bowler RM. Environmental exposure to manganese in air: Tremor, motor and cognitive symptom profiles. Neurotoxicology 2018; 64:152-158. [PMID: 28965701 PMCID: PMC6260785 DOI: 10.1016/j.neuro.2017.09.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Revised: 09/27/2017] [Accepted: 09/27/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND Excessive exposure to manganese (Mn) may cause parkinsonian-like motor and tremor symptoms and adverse cognitive effects, including problems with executive functioning (EF), resembling those found in later-stage Parkinson's disease (PD). Studies seeking to differentiate PD patients into subgroups with associated cognitive and functional outcomes using motor and tremor symptoms identified tremor-dominant (TD) and non-tremor dominant (NTD) subtypes. It is unclear whether differing patterns of pathophysiology and symptoms exist in Mn neurotoxicity, as they do in PD. METHODS Residents of East Liverpool (n=83) and Marietta, OH (n=99) exposed to chronic (>10years) environmental Mn through industrial pollution were administered neuropsychological measures and a physician-rated scale of movement-disorder symptoms. Two-step cluster analysis was used to group residents based on tremor symptoms, bradykinesia/rigidity symptoms, gait disturbance, and executive function. Cluster membership was validated using modeled air-Mn exposure and a computerized tremor measure. RESULTS Elevated tremor and motor symptoms and executive dysfunction were observed, and TD and NTD symptom clusters were identified. Two additional clusters were also identified: Executive Dysfunction and Normal Functioning. The NTD residents, with elevated levels of gait disturbance and other movement disorder symptoms, did not evidence EF impairment, as predicted. Instead, residents with EF impairment formed their own cluster, and were relatively free of movement disorder symptoms. CONCLUSIONS Results resemble reports in the PD literature with TD and NTD clusters identified, but executive dysfunction did not cluster with NTD symptoms. PD and Mn exposure likely have differing pathophysiology and developmental courses, and therefore different symptom patterns, even when similar symptoms are present.
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Affiliation(s)
- E S Kornblith
- San Francisco VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, United States.
| | - S L Casey
- Alliant International University, San Francisco, CA, United States
| | - D T Lobdell
- US EPA, Research Triangle Park, NC, United States
| | - M A Colledge
- Agency for Toxic Substances and Disease Registry, Chicago, Il, United States
| | - R M Bowler
- San Francisco State University, San Francisco, CA, United States
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Du CX, Liu J, Guo Y, Zhang L, Zhang QJ. Lesions of the lateral habenula improve working memory performance in hemiparkinsonian rats. Neurosci Lett 2017; 662:162-166. [PMID: 29054431 DOI: 10.1016/j.neulet.2017.10.027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Revised: 10/15/2017] [Accepted: 10/16/2017] [Indexed: 11/19/2022]
Abstract
The lateral habenula (LHb) is an important structure involved in various brain functions, because it controls the activity of dopaminergic and serotonergic systems in the midbrain. The impairment of working memory commonly occurs in Parkinson's disease; however, it is not clear whether the LHb involves in the regulation of working memory in rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB). In this study, we found that the MFB lesions in rats decreased choice accuracy as measured by the T-maze rewarded alternation test compared to control rats, indicating the induction of working memory impairment, and decreased dopamine (DA) levels in the medial prefrontal cortex (mPFC), hippocampus and amygdala. Further, rats in the MFB and LHb lesion group showed increased choice accuracy compared to rats in the MFB lesion group, indicating the enhancement of working memory after lesioning the LHb. Neurochemical results found that lesions of the LHb increased DA levels in the mPFC, hippocampus and amygdala in the MFB and LHb lesion group, as well as serotonin (5-HT) level in the mPFC. These findings suggest that DA depletion plays a key role in working memory impairment, and lesions of the LHb improve working memory in the MFB-lesioned rats, which involves in increases in the levels of DA and 5-HT in the mPFC, hippocampus and amygdala. Additionally, the present results may have implications for improving our understanding of the neuropathology and/or treatment of PD.
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Affiliation(s)
- Cheng Xue Du
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Yuan Guo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Li Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Qiao Jun Zhang
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
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Laugeray A, Herzine A, Perche O, Richard O, Montecot-Dubourg C, Menuet A, Mazaud-Guittot S, Lesné L, Jegou B, Mortaud S. In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice-An ethological and transcriptomic study. PLoS One 2017; 12:e0184475. [PMID: 29020013 PMCID: PMC5636066 DOI: 10.1371/journal.pone.0184475] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 08/19/2017] [Indexed: 01/03/2023] Open
Abstract
Accumulating evidence suggests that developmental exposure to environmental chemicals may modify the course of brain development, ultimately leading to neuropsychiatric / neurodegenerative disorders later in life. In the present study, we assessed the impact of one of the most frequently used pesticides in both residential and agricultural applications − the synthetic pyrethroid cypermethrin (CYP) − on developmental neurotoxicity (DNT). Female mice were perinatally exposed to low doses of CYP (5 and 20 mg/kg body weight) from gestation to postnatal day 15. Behavioral analyses were performed during the offspring’s early life and during adulthood. Postnatal analyses revealed that perinatal exposure to CYP disturbed motor development without modifying sensory and communicative skills. We found that later in life, CYP-exposed offspring expressed maladaptive behaviors in response to highly challenging tasks and abnormal sociability. Transcriptomic analyses performed in the offspring’s brain at the end of the exposure, highlighted mitochondrial dysfunction as a relevant pathomechanism underlying CYP-induced DNT. Interestingly, several genes involved in proteostasis maintenance were also shown to be dysregulated suggesting that alterations in biogenesis, folding, trafficking and degradation of proteins may significantly contribute to CYP-related DNT. From a regulatory perspective, this study highlights that behavioral and transcriptomic analyses are complementary tools providing useful direction for better DNT characterization, and as such, should be used together more systematically.
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Affiliation(s)
- Anthony Laugeray
- Immunologie et Neurogénétique Expérimentales et Moléculaires – UMR7355 CNRS – Orléans, France
- * E-mail: (AL); (SM)
| | - Ameziane Herzine
- Immunologie et Neurogénétique Expérimentales et Moléculaires – UMR7355 CNRS – Orléans, France
| | - Olivier Perche
- Immunologie et Neurogénétique Expérimentales et Moléculaires – UMR7355 CNRS – Orléans, France
- Département de génétique, Center Hospitalier Régional, Orléans, France
| | - Olivier Richard
- Immunologie et Neurogénétique Expérimentales et Moléculaires – UMR7355 CNRS – Orléans, France
| | - Céline Montecot-Dubourg
- Immunologie et Neurogénétique Expérimentales et Moléculaires – UMR7355 CNRS – Orléans, France
| | - Arnaud Menuet
- Immunologie et Neurogénétique Expérimentales et Moléculaires – UMR7355 CNRS – Orléans, France
| | | | | | - Bernard Jegou
- IRSET INSERM U 1085, Université de Rennes I, Rennes, France
| | - Stéphane Mortaud
- Immunologie et Neurogénétique Expérimentales et Moléculaires – UMR7355 CNRS – Orléans, France
- * E-mail: (AL); (SM)
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Wu ZH, Zhang QJ, Du CX, Xi Y, Li WJ, Guo FY, Yu SQ, Yang YX, Liu J. Prelimbic α1-adrenoceptors are involved in the regulation of depressive-like behaviors in the hemiparkinsonian rats. Brain Res Bull 2017; 134:99-108. [DOI: 10.1016/j.brainresbull.2017.07.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2017] [Revised: 07/04/2017] [Accepted: 07/10/2017] [Indexed: 01/21/2023]
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25
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Wang S, Zhao Y, Gao J, Guo Y, Wang X, Huo J, Wei P, Cao J. In Vivo Effect of a 5-HT 7 Receptor Agonist on 5-HT Neurons and GABA Interneurons in the Dorsal Raphe Nuclei of Sham and PD Rats. Am J Alzheimers Dis Other Demen 2017; 32:73-81. [PMID: 28084087 PMCID: PMC10852805 DOI: 10.1177/1533317516685425] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/03/2024]
Abstract
The 5-hydroxytryptamine (5-HT; serotonin) neurotransmission is severely affected by the degeneration of nigrostriatal dopaminergic neurons. Here, we report the effects of the systemic administration of the 5-HT7 receptor agonist AS-19. In sham rats, the mean response of the 5-HT neurons in the dorsal raphe nucleus (DRN) to systemic AS-19 was excitatory and the mean response of the γ-aminobutyric acid (GABA) interneurons was inhibitory. In Parkinson disease (PD) rats, the same dose did not affect the 5-HT neurons and only high doses (640 μg/kg intravenous) were able to the increase GABA interneuron activity. These results indicate that DRN 5-HT neurons and GABA interneurons are regulated by the activation of 5-HT7 receptors and that the degeneration of the nigrostriatal pathway leads to decreased responses of these neurons to AS-19, which in turn suggests that the 5-HT7 receptors on 5-HT neurons and GABA interneurons in PD rats are dysfunctional and downregulated.
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Affiliation(s)
- Shuang Wang
- Department of Pathophysiology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
| | - Yan Zhao
- Department of Pathophysiology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
| | - Jie Gao
- Department of Pathophysiology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
| | - Yufang Guo
- Department of Pathophysiology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
| | - Xiang Wang
- Department of Pathophysiology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
| | - Jian Huo
- Department of Pathophysiology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
| | - Ping Wei
- Department of Immunology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
| | - Jian Cao
- Department of Physiology, Institute of Basic Medical Science, Xi’an Medical University, Xi’an, China
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Lai SW, Lin CH, Lin HF, Lin CL, Lin CC, Liao KF. Herpes zoster correlates with increased risk of Parkinson's disease in older people: A population-based cohort study in Taiwan. Medicine (Baltimore) 2017; 96:e6075. [PMID: 28207515 PMCID: PMC5319504 DOI: 10.1097/md.0000000000006075] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan.We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model.The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group.Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease.
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Affiliation(s)
- Shih-Wei Lai
- College of Medicine
- Department of Family Medicine
| | | | - Hsien-Feng Lin
- Department of Family Medicine
- College of Chinese Medicine
| | - Cheng-Li Lin
- College of Medicine
- Management Office for Health Data, China Medical University Hospital
| | - Cheng-Chieh Lin
- College of Medicine
- Department of Family Medicine
- Department of Healthcare Administration, College of Health Science, Asia University, Taichung
| | - Kuan-Fu Liao
- College of Medicine, Tzu Chi University, Hualien
- Graduate Institute of Integrated Medicine, China Medical University
- Department of Internal Medicine, Taichung Tzu Chi General Hospital, Taichung, Taiwan
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Wang T, Zhang L, Zhang QJ, Wang Y, Du CX, Sun YN, Zhang J, Lv SX, Chen L, Liu J. Involvement of lateral habenula α1 subunit-containing GABA A receptor-mediated inhibitory transmission in the regulation of depression-related behaviors in experimental Parkinson's disease. Neuropharmacology 2017; 116:399-411. [PMID: 28109827 DOI: 10.1016/j.neuropharm.2017.01.015] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2016] [Revised: 10/27/2016] [Accepted: 01/17/2017] [Indexed: 02/06/2023]
Abstract
The lateral habenula (LHb) plays an important role in the regulation of depression. At present, it is not clear whether GABAA receptor-mediated inhibitory transmission in the LHb is involved in Parkinson's disease (PD)-associated depression. In this study, unilateral 6-hydroxydopamine lesions of the substantia nigra in rats induced depressive-like behaviors and led to hyperactivity of LHb neurons compared to sham-operated rats, which attribute to depletion of dopamine, and decreased synthesis and release of GABA and increased release of glutamate in the LHb. Intra-LHb injection of GABAA receptor agonist muscimol produced antidepressant-like effects, while the injection of GABAA receptor antagonist picrotoxin induced or increased the expression of depressive-like behaviors in sham-operated and the lesioned rats. However, the doses producing these behavioral effects in the lesioned rats were lower than those in sham-operated rats. Intra-LHb injection of muscimol decreased the firing rate of LHb neurons and increased the medial prefrontal cortex serotonin (5-HT) release; conversely, picrotoxin increased the firing rate of the neurons and decreased 5-HT release in two groups of rats. Compared to sham-operated rats, the duration of muscimol and picrotoxin action on the firing rate of the neurons and 5-HT release was prolonged in the lesioned rats. These changes in the lesioned rats were associated with up-regulation of the expression of α1 subunit-containing GABAA receptors and reduction of GABA release in the LHb. Collectively, our findings suggest that degeneration of the nigrostriatal pathway impairs GABAA receptor-mediated inhibitory transmission in the LHb, and the transmission is important for regulating PD-associated depression.
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Affiliation(s)
- Tao Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Li Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China
| | - Qiao-Jun Zhang
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - Yong Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China
| | - Cheng-Xue Du
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Yi-Na Sun
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jin Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Shu-Xuan Lv
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Li Chen
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an 710061, China.
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Torres JAKL, Rosales RL. Nonmotor Symptoms in Dystonia. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2017; 134:1335-1371. [DOI: 10.1016/bs.irn.2017.05.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Gökçal E, Gür VE, Selvitop R, Babacan Yildiz G, Asil T. Motor and Non-Motor Symptoms in Parkinson's Disease: Effects on Quality of Life. Noro Psikiyatr Ars 2016; 54:143-148. [PMID: 28680312 DOI: 10.5152/npa.2016.12758] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Accepted: 02/18/2016] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION This study aimed to evaluate motor and non-motor symptoms in idiopathic Parkinson's disease (IPD) patients and to determine the self-reported influence of all existing symptoms on their quality of life (QoL). METHODS The sociodemographic and clinical characteristics, medical treatments, and Modified Hoehn and Yahr (mH&Y) scores of IPD patients without cognitive impairment were recorded. A survey questioning different motor and non-motor symptoms was administered to the patients. The patients were asked to rate their symptoms by number from the greatest influence to the least influence on their QoL. Subjects were divided into two groups: those suffering from IPD for ≤5 years (Group 1) and those suffering from IPD for >5 years (Group 2). These groups were compared in terms of sociodemographic and clinical characteristics, existing symptoms, and influences of these symptoms on their QoL. RESULTS There were 63 patients in Group 1 and 37 patients in Group 2. No statistically significant differences were detected between the groups with respect to sociodemographic characteristics or mH&Y scores. The most common motor symptoms in both of these groups were tremor and bradykinesia; meanwhile, the non-motor symptoms most frequently encountered in these groups were pain-cramps, constipation, and excessive daytime sleepiness (EDS). Again, while the symptoms that most greatly disturbed QoL in all patients were reported to be tremor and bradykinesia, the most disturbing non-motor symptom was frequent voiding/incontinence, which was a less common symptom. Pain-cramp, constipation, and EDS, which were the most frequent non-motor symptoms, were the symptoms that least disturbed QoL. CONCLUSION It is widely accepted that motor symptoms determine QoL in IPD. However, non-motor symptoms are seen during all phases of the disease. The impact of non-motor symptoms on the QoL of IPD patients remains substantial. Therefore, in addition to the well-known motor symptoms, non-motor symptoms, which may be overlooked during physical examination yet may profoundly impact QoL, should be questioned and treated appropriately to improve QoL in PD patients as much as possible.
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Affiliation(s)
- Elif Gökçal
- Department of Neurology, Bezmialem Vakıf University School of Medicine, İstanbul, Turkey
| | - Veysel Eren Gür
- Department of Neurology, Bezmialem Vakıf University School of Medicine, İstanbul, Turkey
| | - Rabia Selvitop
- Department of Neurology, Bezmialem Vakıf University School of Medicine, İstanbul, Turkey
| | - Gülsen Babacan Yildiz
- Department of Neurology, Bezmialem Vakıf University School of Medicine, İstanbul, Turkey
| | - Talip Asil
- Department of Neurology, Bezmialem Vakıf University School of Medicine, İstanbul, Turkey
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Activation and blockade of prelimbic 5-HT6 receptors produce different effects on depressive-like behaviors in unilateral 6-hydroxydopamine-induced Parkinson's rats. Neuropharmacology 2016; 110:25-36. [DOI: 10.1016/j.neuropharm.2016.07.014] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 07/10/2016] [Accepted: 07/12/2016] [Indexed: 11/15/2022]
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Fereshtehnejad SM. Strategies to maintain quality of life among people with Parkinson's disease: what works? Neurodegener Dis Manag 2016; 6:399-415. [PMID: 27600287 DOI: 10.2217/nmt-2016-0020] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Among chronic neurodegenerative disorders, Parkinson's disease (PD) is one of the most difficult and challenging to tackle as several motor and nonmotor features influence the patients' quality of life (QoL) and daily activities. Assessing patients QoL with valid instruments and gathering knowledge about the determinants that affect QoL in individuals with PD are the basis of an efficient caring strategy. In addition to the known motor symptoms, nonmotor disorders must also be comprehensively tracked and targeted for treatment to enhance QoL. A holistic strategy to maintain QoL in people with PD should consist of a multidisciplinary, personalized and patient-centered approach with timely administration of palliative care and efficient involvement of caregivers and family members.
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Affiliation(s)
- Seyed-Mohammad Fereshtehnejad
- Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences & Society (NVS), Karolinska Institutet, Stockholm, Sweden.,Department of Neurology & Neurosurgery, Faculty of Medicine, McGill University, Montreal General Hospital, Montreal, Québec, Canada
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Dysautonomia Differentially Influences the Effect of Affective Pain Perception on Quality of Life in Parkinson's Disease Patients. PARKINSONS DISEASE 2016; 2016:3067426. [PMID: 27239367 PMCID: PMC4864558 DOI: 10.1155/2016/3067426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Revised: 03/18/2016] [Accepted: 04/11/2016] [Indexed: 11/17/2022]
Abstract
Background. Our aim was to evaluate the real effect of dysautonomic symptoms on the influence of affective pain perception on quality of life in PD patients. Methods. An observational cross-sectional study was carried out using 105 Parkinson's disease (PD) patients of the Movement Disorders Unit, Hospital de Cruces (Bilbao, Spain) [men 59 (56.2%), women 46 (43.85%)]. Statistical analysis was made in order to evaluate the possible association of pain with life quality. Results. Quality of life measured by PDQ-39 (Parkinson's Disease Questionnaire for quality of life) was statistically associated with affective dimension of pain (PRIA, affective pain rating index). However, the influence of this dimension on PDQ-39 was different in the specific case of PD patients that experimented a high score (>12) in SCOPA-AUT (Scale for Outcomes in PD-Autonomic scale). Conclusions. These results confirm the effect of affective perception of pain in life quality of PD patients, indicating the critical role of autonomic symptoms in the modulation of the influence of pain on quality of life and showing the possible utility of dysautonomia as clinical prognostic indicator of quality of life in PD patients affected by pain.
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Han LN, Zhang L, Sun YN, Du CX, Zhang YM, Wang T, Zhang J, Liu J. Serotonin7 receptors in the lateral habenular nucleus regulate depressive-like behaviors in the hemiparkinsonian rats. Brain Res 2016; 1644:79-87. [PMID: 27178363 DOI: 10.1016/j.brainres.2016.05.016] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 05/07/2016] [Accepted: 05/09/2016] [Indexed: 01/21/2023]
Abstract
Preclinical studies indicate that serotonin7 (5-HT7) receptors may regulate depressive-like behaviors. Depression is a common symptom in Parkinson's disease (PD); however, its pathophysiology is unclear. Here we examined whether 5-HT7 receptors in the lateral habenular nucleus (LHb) involve in the regulation of PD-related depression. Unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta in rats induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. Intra-LHb injection of 5-HT7 receptor agonist AS19 (1, 2 and 4μg/rat) induced or increased the expression of depressive-like behaviors in sham-operated and the lesioned rats. Further, intra-LHb injection of 5-HT7 receptor antagonist SB269970 (1.5, 3 and 6μg/rat) produced antidepressant effects in the two groups of rats. However, the doses producing these effects in the lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-LHb injection of AS19 (4μg/rat) decreased dopamine and 5-HT levels in the medial prefrontal cortex, habenula and hippocampus in sham-operated and the lesioned rats; whereas SB269970 (6μg/rat) increased dopamine and 5-HT levels in these structures. In addition, noradrenaline levels in these structures were not changed after intra-LHb injection of AS19 or SB269970 in the two groups of rats. These findings suggest that activation or blockade of 5-HT7 receptors in the LHb may change the activity of LHb glutamate neurons, and then decreases or increases dopamine and 5-HT levels in the limbic and limbic-related brain regions, which are involved in the regulation of depressive-like behaviors.
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Affiliation(s)
- Ling Na Han
- Department of Physiology, Changzhi Medical College, Changzhi 046000, China
| | - Li Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Yi Na Sun
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Cheng Xue Du
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Yu Ming Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Tao Wang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jin Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
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Thurm F, Schuck NW, Fauser M, Doeller CF, Stankevich Y, Evens R, Riedel O, Storch A, Lueken U, Li SC. Dopamine modulation of spatial navigation memory in Parkinson's disease. Neurobiol Aging 2016; 38:93-103. [DOI: 10.1016/j.neurobiolaging.2015.10.019] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 10/15/2015] [Accepted: 10/23/2015] [Indexed: 01/13/2023]
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Janakiraman U, Manivasagam T, Thenmozhi AJ, Essa MM, Barathidasan R, SaravanaBabu C, Guillemin GJ, Khan MAS. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice. PLoS One 2016; 11:e0146671. [PMID: 26765842 PMCID: PMC4713092 DOI: 10.1371/journal.pone.0146671] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Accepted: 12/21/2015] [Indexed: 12/31/2022] Open
Abstract
Parkinson's disease (PD) is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic) neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS) such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS), a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt.) with probenecid (250 mg/kg, s.c.) (MPTP/p) induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks) of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor) impairments, levels and expressions of dopamine (DA), serotonin (5-HT), DAergic markers such as tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporters-2 (VMAT 2) and α-synuclein in nigrostriatal (striatum (ST) and substantia nigra (SN)) and extra-nigrostriatal (hippocampus, cortex and cerebellum) tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.
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Affiliation(s)
- Udaiyappan Janakiraman
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India
| | - Thamilarasan Manivasagam
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India
- * E-mail:
| | - Arokiasamy Justin Thenmozhi
- Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, 608002, Tamilnadu, India
| | - Musthafa Mohamed Essa
- Department of Food Science and Nutrition, CAMS, Sultan Qaboos University, Muscat, Oman
- Ageing and Dementia Research Group, Sultan Qaboos University, Muscat, Oman
| | - Rajamani Barathidasan
- Centre for Toxicology and Developmental Research, Sri Ramachandra University, Porur, Chennai-600 116, Tamilnadu, India
| | - Chidambaram SaravanaBabu
- Centre for Toxicology and Developmental Research, Sri Ramachandra University, Porur, Chennai-600 116, Tamilnadu, India
| | - Gilles J. Guillemin
- Neuropharmacology group, Faculty of Medicine and Health Sciences, Deb Bailey MND Research Laboratory, Macquarie University, NSW, 2109, Australia
| | - Mohammed A. S. Khan
- Harvard Medical School, Massachusetts General Hospital, Shriners Hospital for Children, Boston, Massachusetts, 02114, United States of America
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Ghanbari M, Darweesh SK, de Looper HW, van Luijn MM, Hofman A, Ikram MA, Franco OH, Erkeland SJ, Dehghan A. Genetic Variants in MicroRNAs and Their Binding Sites Are Associated with the Risk of Parkinson Disease. Hum Mutat 2015; 37:292-300. [DOI: 10.1002/humu.22943] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 12/04/2015] [Indexed: 12/21/2022]
Affiliation(s)
- Mohsen Ghanbari
- Department of Epidemiology; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
- Department of Genetics, School of Medicine; Mashhad University of Medical Sciences; Mashhad Iran
| | - Sirwan K.L. Darweesh
- Department of Epidemiology; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
| | - Hans W.J. de Looper
- Department of Hematology, Erasmus University Medical Center; Cancer Institute; Rotterdam 3000 CA The Netherlands
| | - Marvin M. van Luijn
- Department of Immunology, MS Center ErasMS; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
| | - Albert Hofman
- Department of Epidemiology; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
- Department of Epidemiology; Harvard T.H. Chan School of Public Health; Boston Mass USA
| | - M. Arfan Ikram
- Department of Epidemiology; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
| | - Oscar H. Franco
- Department of Epidemiology; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
| | - Stefan J. Erkeland
- Department of Immunology; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
| | - Abbas Dehghan
- Department of Epidemiology; Erasmus University Medical Center; Rotterdam 3000 CA The Netherlands
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Quality of life in patients with PD and their caregiving spouses: A view from both sides. Clin Neurol Neurosurg 2015; 139:24-8. [DOI: 10.1016/j.clineuro.2015.08.027] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Revised: 04/01/2015] [Accepted: 08/22/2015] [Indexed: 11/19/2022]
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Zhang QJ, Du CX, Tan HH, Zhang L, Li LB, Zhang J, Niu XL, Liu J. Activation and blockade of serotonin7 receptors in the prelimbic cortex regulate depressive-like behaviors in a 6-hydroxydopamine-induced Parkinson's disease rat model. Neuroscience 2015; 311:45-55. [PMID: 26470809 DOI: 10.1016/j.neuroscience.2015.10.016] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 09/16/2015] [Accepted: 10/08/2015] [Indexed: 01/27/2023]
Abstract
The role of serotonin7 (5-HT7) receptors in the regulation of depression is poorly understood, particularly in Parkinson's disease-associated depression. Here we examined whether 5-HT7 receptors in the prelimbic (PrL) sub-region of the ventral medial prefrontal cortex (mPFC) involve in the regulation of depressive-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. The lesion induced depressive-like responses as measured by the sucrose preference and forced swim tests when compared to sham-operated rats. Intra-PrL injection of 5-HT7 receptor agonist AS19 (0.5, 1 and 2 μg/rat) increased sucrose consumption, and decreased immobility time in sham-operated and the lesioned rats, indicating the induction of antidepressant-like effects. Further, intra-PrL injection of 5-HT7 receptor antagonist SB269970 (1.5, 3 and 6 μg/rat) decreased sucrose consumption, and increased immobility time, indicating the induction of depressive-like responses. However, the doses producing these effects in the lesioned rats were higher than those in sham-operated rats. Neurochemical results showed that intra-PrL injection of AS19 (2 μg/rat) increased dopamine, 5-hydroxytryptamine (5-HT) and noradrenaline (NA) levels in the mPFC, habenula and ventral hippocampus (vHip) in sham-operated and the lesioned rats; whereas SB269970 (6 μg/rat) decreased 5-HT levels in the habenula and vHip, and the levels of NA in the mPFC, habenula and vHip in the two groups of rats. The results suggest that 5-HT7 receptors in the PrL play an important role in the regulation of these behaviors, which attribute to changes in monoamine levels in the limbic and limbic-related brain regions after activation and blockade of 5-HT7 receptors.
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Affiliation(s)
- Q J Zhang
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - C X Du
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - H H Tan
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - L Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - L B Li
- Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - J Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - X L Niu
- Department of Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - J Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
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Han LN, Zhang L, Li LB, Sun YN, Wang Y, Chen L, Guo Y, Zhang YM, Zhang QJ, Liu J. Activation of serotonin(2C) receptors in the lateral habenular nucleus increases the expression of depression-related behaviors in the hemiparkinsonian rat. Neuropharmacology 2015; 93:68-79. [PMID: 25661701 DOI: 10.1016/j.neuropharm.2015.01.024] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Revised: 01/21/2015] [Accepted: 01/26/2015] [Indexed: 11/24/2022]
Abstract
The roles of lateral habenular nucleus (LHb) glutamate neurons and serotonin2C (5-HT2C) receptors in depression are poorly understood, particularly in Parkinson's disease-associated depression. Here we assessed the importance of LHb glutamate neurons and 5-HT2C receptors for depressive-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine lesions of the substantia nigra. The lesion induced depressive-like responses compared to sham-operated rats. Intra-LHb injection of potent, selective 5-HT2C receptor agonist Ro60-0175 decreased sucrose consumption and increased immobility time in sham-operated rats, indicating the induction of depressive-like responses, and intra-LHb injection of Ro60-0175 further increased the expression of depressive-like behaviors in the lesioned rats. Activation of LHb 5-HT2C receptors by the local administration of Ro60-0175 increased the firing rate of EAAC1 (a neuronal glutamate transporter)-positive neurons and percentage of the neurons with burst-firing pattern in the two groups of rats. Compared to sham-operated rats, the duration of Ro60-0175 action on the firing rate of EAAC1-positive neurons was markedly prolonged in the lesioned rats. Intra-LHb injection of Ro60-0175 decreased dopamine, 5-HT and noradrenaline levels in the medial prefrontal cortex, habenula, hippocampus and amygdala in sham-operated and the lesioned rats. The lesion did not change the percentage of EAAC1/5-HT2C receptor co-expressing neurons in the LHb. These findings indicate that activation of 5-HT2C receptors in the LHb increases firing activity of LHb glutamate neurons and then decreases monoamine levels in several brain regions, which increase the expression of depressive-like behaviors. Further, our results also suggest that the lesion leads to hyperfunctionality of 5-HT2C receptors on glutamate neurons of the LHb.
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Affiliation(s)
- Ling-Na Han
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
| | - Li Zhang
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
| | - Li-Bo Li
- Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - Yi-Na Sun
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yong Wang
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
| | - Li Chen
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yuan Guo
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yu-Ming Zhang
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
| | - Qiao-Jun Zhang
- Department of Rehabilitation Medicine, the Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
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Lai SW, Lin CL, Liao KF, Chang-Ou KC. Increased risk of Parkinson's disease in cataract patients: A population-based cohort study. Parkinsonism Relat Disord 2015; 21:68-71. [DOI: 10.1016/j.parkreldis.2014.11.005] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Revised: 11/06/2014] [Accepted: 11/07/2014] [Indexed: 12/23/2022]
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Lewis CJ, Maier F, Horstkötter N, Zywczok A, Witt K, Eggers C, Meyer TD, Dembek TA, Maarouf M, Moro E, Zurowski M, Woopen C, Kuhn J, Timmermann L. Subjectively perceived personality and mood changes associated with subthalamic stimulation in patients with Parkinson's disease. Psychol Med 2015; 45:73-85. [PMID: 25066623 DOI: 10.1017/s0033291714001081] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Clinical and ethical implications of personality and mood changes in Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS) are under debate. Although subjectively perceived personality changes are often mentioned by patients and caregivers, few empirical studies concerning these changes exist. Therefore, we analysed subjectively perceived personality and mood changes in STN-DBS PD patients. METHOD In this prospective study of the ELSA-DBS group, 27 PD patients were assessed preoperatively and 1 year after STN-DBS surgery. Two categories, personality and mood changes, were analysed with semi-structured interviews. Patients were grouped into personality change yes/no, as well as positive/negative mood change groups. Caregivers were additionally interviewed about patients' personality changes. Characteristics of each group were assessed with standard neurological and psychiatric measurements. Predictors for changes were analysed. RESULTS Personality changes were perceived by six of 27 (22%) patients and by 10 of 23 caregivers (44%). The preoperative hypomania trait was a significant predictor for personality change perceived by patients. Of 21 patients, 12 (57%) perceived mood as positively changed. Higher apathy and anxiety ratings were found in the negative change group. CONCLUSIONS Our results show that a high proportion of PD patients and caregivers perceived personality changes under STN-DBS, emphasizing the relevance of this topic. Mood changed in positive and negative directions. Standard measurement scales failed to adequately reflect personality or mood changes subjectively perceived by patients. A more individualized preoperative screening and preparation for patients and caregivers, as well as postoperative support, could therefore be useful.
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Affiliation(s)
- C J Lewis
- Department of Neurology,University of Cologne,Cologne,Germany
| | - F Maier
- Department of Neurology,University of Cologne,Cologne,Germany
| | - N Horstkötter
- Research Unit Ethics, Institute for the History of Medicine and Medical Ethics,University of Cologne,Cologne,Germany
| | - A Zywczok
- Department of Neurology,University of Cologne,Cologne,Germany
| | - K Witt
- Research Unit Ethics, Institute for the History of Medicine and Medical Ethics,University of Cologne,Cologne,Germany
| | - C Eggers
- Department of Neurology,University of Cologne,Cologne,Germany
| | - T D Meyer
- Institute of Neuroscience,Newcastle University,Newcastle upon Tyne,UK
| | - T A Dembek
- Department of Neurology,University of Cologne,Cologne,Germany
| | - M Maarouf
- Department of Stereotaxy and Functional Neurosurgery,University of Cologne,Cologne,Germany
| | - E Moro
- Movement Disorders Unit, Department of Psychiatry and Neurology,University Hospital Center (CHU) of Grenoble,Grenoble,France
| | - M Zurowski
- Department of Psychiatry,University of Toronto, University Health Network,Toronto,Canada
| | - C Woopen
- Research Unit Ethics, Institute for the History of Medicine and Medical Ethics,University of Cologne,Cologne,Germany
| | - J Kuhn
- Department of Psychiatry and Psychotherapy,University of Cologne,Cologne,Germany
| | - L Timmermann
- Department of Neurology,University of Cologne,Cologne,Germany
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Cremer JN, Amunts K, Graw J, Piel M, Rösch F, Zilles K. Neurotransmitter receptor density changes in Pitx3ak mice--a model relevant to Parkinson's disease. Neuroscience 2014; 285:11-23. [PMID: 25451278 DOI: 10.1016/j.neuroscience.2014.10.050] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2014] [Revised: 10/17/2014] [Accepted: 10/22/2014] [Indexed: 12/16/2022]
Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by alterations of nigrostriatal dopaminergic neurotransmission. Compared to the wealth of data on the impairment of the dopamine system, relatively limited evidence is available concerning the role of major non-dopaminergic neurotransmitter systems in PD. Therefore, we comprehensively investigated the density and distribution of neurotransmitter receptors for glutamate, GABA, acetylcholine, adrenaline, serotonin, dopamine and adenosine in brains of homozygous aphakia mice being characterized by mutations affecting the Pitx3 gene. This genetic model exhibits crucial hallmarks of PD on the neuropathological, symptomatic and pharmacological level. Quantitative receptor autoradiography was used to characterize 19 different receptor binding sites in eleven brain regions in order to understand receptor changes on a systemic level. We demonstrated striking differential changes of neurotransmitter receptor densities for numerous receptor types and brain regions, respectively. Most prominent, a strong up-regulation of GABA receptors and associated benzodiazepine binding sites in different brain regions and concomitant down-regulations of striatal nicotinic acetylcholine and serotonergic receptor densities were found. Furthermore, the densities of glutamatergic kainate, muscarinic acetylcholine, adrenergic α1 and dopaminergic D2/D3 receptors were differentially altered. These results present novel insights into the expression of neurotransmitter receptors in Pitx3(ak) mice supporting findings on PD pathology in patients and indicating on the possible underlying mechanisms. The data suggest Pitx3(ak) mice as an appropriate new model to investigate the role of neurotransmitter receptors in PD. Our study highlights the relevance of non-dopaminergic systems in PD and for the understanding of its molecular pathology.
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Affiliation(s)
- J N Cremer
- Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital, RWTH Aachen University, and JARA - Translational Brain Medicine, D-52062 Aachen, Germany.
| | - K Amunts
- Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany; Cécile & Oskar Vogt Institute of Brain Research, Heinrich-Heine University Düsseldorf, University Hospital Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany
| | - J Graw
- Helmholtz Center Munich, Institute of Developmental Genetics (IDG), Ingolstaedter Landstraße 1, D-85764 Neuherberg, Germany
| | - M Piel
- Institute of Nuclear Chemistry, Johannes Gutenberg University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz, Germany
| | - F Rösch
- Institute of Nuclear Chemistry, Johannes Gutenberg University of Mainz, Fritz-Strassmann-Weg 2, D-55128 Mainz, Germany
| | - K Zilles
- Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, D-52425 Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital, RWTH Aachen University, and JARA - Translational Brain Medicine, D-52062 Aachen, Germany
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Ota K, Iseki E, Murayama N, Chiba Y, Fujishiro H, Kasanuki K, Manabe Y, Arai H, Sato K. Three presenile patients in which neuropsychological and neuroimaging examinations suggest possible progression to dementia with Lewy bodies. Psychogeriatrics 2014; 14:72-80. [PMID: 24528622 DOI: 10.1111/psyg.12039] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Revised: 10/29/2013] [Accepted: 12/12/2013] [Indexed: 11/30/2022]
Abstract
We report three presenile patients who were initially suspected of having Alzheimer's disease (AD) or being in the prodromal stage of AD, regardless of visuoperceptual dysfunctions in daily living, because they lacked the core features and prodromal non-motor symptoms of dementia with Lewy bodies. Subsequently, progression to dementia with Lewy bodies was suspected based on neuropsychological and neuroimaging findings; additionally, one of the three patients suffered from visual hallucinations. Neuropsychological examinations such as subjective contours, cube copying and block design in the Wechsler Adult Intelligence Scale-III revealed visuoperceptual dysfunction in all three patients even when other cognitive functions were rather preserved. Brain magnetic resonance imaging revealed no significant brain atrophy, including in the parieto-occipital area and the hippocampus, while brain (18)F-fluorodeoxyglucose positron emission tomography demonstrated right dominant metabolic reductions in the occipital lobe, including the primary visual cortex, in all three patients. We suggest the possibility of progression to dementia with Lewy bodies, but not AD or posterior cortical atrophy. Regardless of the presence of core features and prodromal non-motor symptoms, this progression is suggested when there are difficulties only in higher-level visual processing such as subjective contours and block design in the Wechsler Adult Intelligence Scale-III, no significant atrophy of the parieto-occipital area and hippocampus on brain magnetic resonance imaging, and hypometabolism in the occipital lobe including the primary visual cortex on brain (18)F-fluorodeoxyglucose positron emission tomography.
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Affiliation(s)
- Kazumi Ota
- PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center, Juntendo University School of Medicine, Tokyo, Japan
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Abstract
Parkinson's disease (PD) is, after Alzheimer's disease, the second most common neurodegenerative disorder with an approximate prevalence of 0.5-1% among persons 65-69 years of age, rising to 1-3% among persons 80 years of age and older. Pathologically, PD is characterized by the loss of neurons in the substantia nigra pars compacta (SNpc), and by the presence of eosinophilic protein deposits (Lewy bodies) in this region, in other aminergic nuclei and in cortical and limbic structures. Moreover, it has now been shown that pathology also involves the peripheral nervous system. Braak and colleagues suggested a thread of pathology starting from the vagal nerve to progress to the brainstem, and eventually to limbic and neocortical brain regions. This progression of pathology may account for the clinical evolution of PD toward a composite symptomatology. However, this hypothesis has been criticized by others. In this chapter, we review the clinical features of PD (motor and nonmotor) and their pathological correlates.
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Depressione e malattia di Parkinson. Neurologia 2013. [DOI: 10.1016/s1634-7072(12)63928-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Neurologists' diagnostic accuracy of depression and cognitive problems in patients with parkinsonism. BMC Neurol 2012; 12:37. [PMID: 22702891 PMCID: PMC3465198 DOI: 10.1186/1471-2377-12-37] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2011] [Accepted: 05/18/2012] [Indexed: 12/18/2022] Open
Abstract
Background Depression and cognitive impairment (CI) are important non-motor symptoms in Parkinson’s Disease (PD) and related syndromes, but it is not clear how well they are recognised in daily practice. We have studied the diagnostic performance of experienced neurologists on the topics depression and cognitive impairment during a routine encounter with a patient with recent-onset parkinsonian symptoms. Methods Two experienced neurologists took the history and examined 104 patients with a recent-onset parkinsonian disorder, and assessed the presence of depression and cognitive impairment. On the same day, all patients underwent a Hamilton Depression Rating Scale test, and a Scales for Outcomes in Parkinson’s Disease-Cognition-test (SCOPA-COG). Results The sensitivity of the neurologists for the topic depression was poor: 33.3%. However, the specificity varied from 90.8 to 94.7%. The patients’ sensitivity was higher, although the specificity was lower. On the topic CI, the sensitivity of the neurologists was again low, in a range from 30.4 up to 34.8%: however the specificity was high, with 92.9%. The patients’ sensitivity and specificity were both lower, compared to the number of the neurologists. Conclusions Neurologists’ intuition and clinical judgment alone are not accurate for detection of depression or cognitive impairment in patients with recent-onset parkinsonian symptoms because of low sensitivity despite of high specificity. Trial registration (ITRSCC)NCT0036819.
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Del Tredici K, Braak H. Lewy pathology and neurodegeneration in premotor Parkinson's disease. Mov Disord 2012; 27:597-607. [DOI: 10.1002/mds.24921] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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Schulte EC, Winkelmann J. When Parkinson's disease patients go to sleep: specific sleep disturbances related to Parkinson's disease. J Neurol 2012; 258:S328-35. [PMID: 21560064 DOI: 10.1007/s00415-011-5933-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Nonmotor symptoms of Parkinson's disease can be as disabling as the much better studied motor symptoms. Among the nonmotor manifestations are numerous forms of alterations of physiologic sleep patterns that may present at different stages during the course of disease. These include changes believed to be primarily related to the underlying neurodegenerative process of the disease as well as those brought about secondarily, for example, by pharmacologic treatment. Also, sleep disturbances seen in Parkinson's disease can range from temporarily increased daytime sleepiness after introduction of a dopamine agonist to the therapeutic regime to specific sleep-related diagnoses such as restless legs syndrome, rapid eye movement sleep behavior disorder, periodic limb movements in sleep, and sleep-related breathing disorders such as obstructive sleep apnea. In this review, we discuss the different specific sleep disturbances that arise in the context of Parkinson's disease with a special emphasis on epidemiology, pathophysiology, and diagnosis.
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Affiliation(s)
- Eva C Schulte
- Neurologische Klinik und Poliklinik, Klinkum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany
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Abstract
This article considers the practicality and patient benefits of transferring evidence-based sleep management skills to community health professionals. Sleep disturbances are among the most frequently reported and poorly managed non-motor symptoms in Parkinson's. But, despite their prevalence, sleep problems in Parkinson's are often under-recognized, under-diagnosed and inadequately treated. To raise awareness and improve patient care in Parkinson's, a three-day sleep management course was developed for Parkinson's disease nurse specialists (PDNSs) practising within NHS Scotland. The course aimed to transfer skills in health education as applied to sleep and insomnia; the assessment of sleep; the practice of sleep hygiene; delivering relaxation methods; the use of stimulus control and sleep restriction procedures; and cognitive approaches to insomnia management. Between June 2010 and July 2011, 38 PDNSs and practising occupational therapists undertook the course. Interviews and evaluations with patients and professionals were carried out afterwards. Patients reported a reduction in anxiety over sleep problems, feeling able to manage their sleep, and having a sense of control over their sleep. Programme outcomes suggest that the training model used is feasible and practical; the resources designed for clinical use are practical and relevant; and that the initiative as a whole represents a valid and affordable investment in patient wellbeing.
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Abstract
Chronic pain is a frequent component of many neurological disorders, affecting 20-40% of patients for many primary neurological diseases. These diseases result from a wide range of pathophysiologies including traumatic injury to the central nervous system, neurodegeneration and neuroinflammation, and exploring the aetiology of pain in these disorders is an opportunity to achieve new insight into pain processing. Whether pain originates in the central or peripheral nervous system, it frequently becomes centralized through maladaptive responses within the central nervous system that can profoundly alter brain systems and thereby behaviour (e.g. depression). Chronic pain should thus be considered a brain disease in which alterations in neural networks affect multiple aspects of brain function, structure and chemistry. The study and treatment of this disease is greatly complicated by the lack of objective measures for either the symptoms or the underlying mechanisms of chronic pain. In pain associated with neurological disease, it is sometimes difficult to obtain even a subjective evaluation of pain, as is the case for patients in a vegetative state or end-stage Alzheimer's disease. It is critical that neurologists become more involved in chronic pain treatment and research (already significant in the fields of migraine and peripheral neuropathies). To achieve this goal, greater efforts are needed to enhance training for neurologists in pain treatment and promote greater interest in the field. This review describes examples of pain in different neurological diseases including primary neurological pain conditions, discusses the therapeutic potential of brain-targeted therapies and highlights the need for objective measures of pain.
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Affiliation(s)
- David Borsook
- MD Center for Pain and the Brain C/O Brain Imaging Center, McLean Hospital Belmont, MA 02478, USA.
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