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Bergamasco MI, Ozturk E, Casillas-Espinosa PM, Garnham AL, Abeysekera W, Wimmer VC, Rajasekhar P, Vanyai HK, Whitehead L, Blewitt ME, Rogers K, Vogel AP, Hannan AJ, Smyth GK, Jones NC, Thomas T, Voss AK. KAT6B overexpression in mice causes aggression, anxiety, and epilepsy. iScience 2025; 28:111953. [PMID: 40083716 PMCID: PMC11904597 DOI: 10.1016/j.isci.2025.111953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 10/20/2024] [Accepted: 01/31/2025] [Indexed: 03/16/2025] Open
Abstract
Loss of the gene encoding the histone acetyltransferase KAT6B (MYST4/MORF/QKF) causes developmental brain abnormalities as well as behavioral and cognitive defects in mice. In humans, heterozygous variants in the KAT6B gene cause two cognitive disorders, Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS; OMIM:603736) and genitopatellar syndrome (GTPTS; OMIM:606170). Although the effects of KAT6B homozygous and heterozygous mutations have been documented in humans and mice, KAT6B gain-of-function effects have not been reported. Here, we show that overexpression of the Kat6b gene in mice caused aggression, anxiety, and spontaneous epilepsy. Kat6b overexpression led to an increase in histone H3 lysine 9 acetylation and upregulation of genes driving nervous system development and neuronal differentiation. Kat6b overexpression additionally promoted neural stem cell proliferation and favored neuronal over astrocyte differentiation in vivo and in vitro. Our results suggest that, in addition to loss-of-function alleles, gain-of-function KAT6B alleles may be detrimental for brain development.
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Affiliation(s)
- Maria I. Bergamasco
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Ezgi Ozturk
- Department of Medicine (Royal Melbourne Hospital), Melbourne Brain Centre, University of Melbourne, Parkville VIC 3052, Australia
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
- Department of Neurology, Alfred Hospital, Melbourne, Melbourne, VIC 3004, Australia
| | - Pablo M. Casillas-Espinosa
- Department of Medicine (Royal Melbourne Hospital), Melbourne Brain Centre, University of Melbourne, Parkville VIC 3052, Australia
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
- Department of Neurology, Alfred Hospital, Melbourne, Melbourne, VIC 3004, Australia
| | - Alexandra L. Garnham
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Waruni Abeysekera
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Verena C. Wimmer
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Pradeep Rajasekhar
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Hannah K. Vanyai
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Lachlan Whitehead
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Marnie E. Blewitt
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Kelly Rogers
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Adam P. Vogel
- Centre for Neurosciences of Speech, The University of Melbourne, Melbourne, VIC 3052, Australia
- Redenlab Inc, Melbourne, VIC 3000, Australia
| | - Anthony J. Hannan
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3010, Australia
- Department of Anatomy and Physiology, University of Melbourne, Parkville, VIC 3010, Australia
| | - Gordon K. Smyth
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia
| | - Nigel C. Jones
- Department of Medicine (Royal Melbourne Hospital), Melbourne Brain Centre, University of Melbourne, Parkville VIC 3052, Australia
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia
- Department of Neurology, Alfred Hospital, Melbourne, Melbourne, VIC 3004, Australia
| | - Tim Thomas
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
| | - Anne K. Voss
- The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia
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Hillerer KM, Gimsa U. Adult neurogenesis and the microbiota-gut-brain axis in farm animals: underestimated and understudied parameters for improving welfare in livestock farming. Front Neurosci 2024; 18:1493605. [PMID: 39664450 PMCID: PMC11631930 DOI: 10.3389/fnins.2024.1493605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 11/05/2024] [Indexed: 12/13/2024] Open
Abstract
Welfare in commercial livestock farming is becoming increasingly important in current agriculture research. Unfortunately, there is a lack of understanding about the neuronal mechanisms that underlie well-being on an individual level. Neuroplasticity in the hippocampus, the subventricular zone (SVZ), the olfactory bulb (OB) and the hypothalamus may be essential regulatory components in the context of farm animal behaviour and welfare that may be altered by providing environmental enrichment (EE). The importance of pre-and probiotics as a form of EE and the microbiota-gut-brain axis (MGBA) has come under the spotlight in the last 20 years, particularly in the contexts of research into stress and of stress resilience. However, it could also be an important regulatory system for animal welfare in livestock farming. This review aims to present a brief overview of the effects of EE on physiology and behaviour in farm animals and briefly discusses literature on behavioural flexibility, as well as inter-individual stress-coping styles and their relationship to animal welfare. Most importantly, we will summarise the literature on different forms of neural plasticity in farm animals, focusing on neurogenesis in various relevant brain regions. Furthermore, we will provide a brief outlook connecting these forms of neuroplasticity, stress, EE, the MGBA and welfare measures in modern livestock farming, concentrating on pigs.
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Affiliation(s)
- Katharina M. Hillerer
- Research Institute for Farm Animal Biology (FBN), Dummerstorf, Mecklenburg-Vorpommern, Germany
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Sorrells SF. Which neurodevelopmental processes continue in humans after birth? Front Neurosci 2024; 18:1434508. [PMID: 39308952 PMCID: PMC11412957 DOI: 10.3389/fnins.2024.1434508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 08/09/2024] [Indexed: 09/25/2024] Open
Abstract
Once we are born, the number and location of nerve cells in most parts of the brain remain unchanged. These types of structural changes are therefore a significant form of flexibility for the neural circuits where they occur. In humans, the postnatal birth of neurons is limited; however, neurons do continue to migrate into some brain regions throughout infancy and even into adolescence. In human infants, multiple migratory pathways deliver interneurons to destinations across the frontal and temporal lobe cortex. Shorter-range migration of excitatory neurons also appears to continue during adolescence, particularly near the amygdala paralaminar nucleus, a region that follows a delayed trajectory of growth from infancy to adulthood. The significance of the timing for when different brain regions recruit new neurons through these methods is unknown; however, both processes of protracted migration and maturation are prominent in humans. Mechanisms like these that reconfigure neuronal circuits are a substrate for critical periods of plasticity and could contribute to distinctive circuit functionality in human brains.
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Herman J, Rittenhouse N, Mandino F, Majid M, Wang Y, Mezger A, Kump A, Kadian S, Lake EMR, Verardi PH, Conover JC. Ventricular-subventricular zone stem cell niche adaptations in a mouse model of post-infectious hydrocephalus. Front Neurosci 2024; 18:1429829. [PMID: 39145299 PMCID: PMC11322059 DOI: 10.3389/fnins.2024.1429829] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 07/02/2024] [Indexed: 08/16/2024] Open
Abstract
Congenital post-infectious hydrocephalus (PIH) is a condition characterized by enlargement of the ventricular system, consequently imposing a burden on the associated stem cell niche, the ventricular-subventricular zone (V-SVZ). To investigate how the V-SVZ adapts in PIH, we developed a mouse model of influenza virus-induced PIH based on direct intracerebroventricular injection of mouse-adapted influenza virus at two distinct time points: embryonic day 16 (E16), when stem cells line the ventricle, and postnatal day 4 (P4), when an ependymal monolayer covers the ventricle surface and stem cells retain only a thin ventricle-contacting process. Global hydrocephalus with associated regions of astrogliosis along the lateral ventricle was found in 82% of the mice infected at P4. Increased ependymogenesis was observed at gliotic borders and throughout areas exhibiting intact ependyma based on tracking of newly divided cells. Additionally, in areas of intact ependyma, stem cell numbers were reduced; however, we found no significant reduction in new neurons reaching the olfactory bulb following onset of ventriculomegaly. At P4, injection of only the non-infectious viral component neuraminidase resulted in limited, region-specific ventriculomegaly due to absence of cell-to-cell transmission. In contrast, at E16 intracerebroventricular injection of influenza virus resulted in death at birth due to hypoxia and multiorgan hemorrhage, suggesting an age-dependent advantage in neonates, while the viral component neuraminidase resulted in minimal, or no, ventriculomegaly. In summary, we tracked acute adaptations of the V-SVZ stem cell niche following onset of ventriculomegaly and describe developmental changes that help mitigate the severity of congenital PIH.
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Affiliation(s)
- Julianna Herman
- Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, United States
| | - Nicole Rittenhouse
- Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, United States
| | - Francesca Mandino
- Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States
| | - Mushirah Majid
- Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, United States
| | - Yuxiang Wang
- Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United States
| | - Amelia Mezger
- Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, United States
| | - Aidan Kump
- Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, United States
| | - Sumeet Kadian
- Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, United States
| | - Evelyn M. R. Lake
- Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, United States
- Department of Biomedical Engineering, Yale University, New Haven, CT, United States
- Wu Tsai Institute, Yale University, New Haven, CT, United States
| | - Paulo H. Verardi
- Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, United States
| | - Joanne C. Conover
- Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT, United States
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Wetzel A, Lei SH, Liu T, Hughes MP, Peng Y, McKay T, Waddington SN, Grannò S, Rahim AA, Harvey K. Dysregulated Wnt and NFAT signaling in a Parkinson's disease LRRK2 G2019S knock-in model. Sci Rep 2024; 14:12393. [PMID: 38811759 PMCID: PMC11137013 DOI: 10.1038/s41598-024-63130-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 05/24/2024] [Indexed: 05/31/2024] Open
Abstract
Parkinson's disease (PD) is a progressive late-onset neurodegenerative disease leading to physical and cognitive decline. Mutations of leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of PD. LRRK2 is a complex scaffolding protein with known regulatory roles in multiple molecular pathways. Two prominent examples of LRRK2-modulated pathways are Wingless/Int (Wnt) and nuclear factor of activated T-cells (NFAT) signaling. Both are well described key regulators of immune and nervous system development as well as maturation. The aim of this study was to establish the physiological and pathogenic role of LRRK2 in Wnt and NFAT signaling in the brain, as well as the potential contribution of the non-canonical Wnt/Calcium pathway. In vivo cerebral Wnt and NFATc1 signaling activity was quantified in LRRK2 G2019S mutant knock-in (KI) and LRRK2 knockout (KO) male and female mice with repeated measures over 28 weeks, employing lentiviral luciferase biosensors, and analyzed using a mixed-effect model. To establish spatial resolution, we investigated tissues, and primary neuronal cell cultures from different brain regions combining luciferase signaling activity, immunohistochemistry, qPCR and western blot assays. Results were analyzed by unpaired t-test with Welch's correction or 2-way ANOVA with post hoc corrections. In vivo Wnt signaling activity in LRRK2 KO and LRRK2 G2019S KI mice was increased significantly ~ threefold, with a more pronounced effect in males (~ fourfold) than females (~ twofold). NFATc1 signaling was reduced ~ 0.5-fold in LRRK2 G2019S KI mice. Brain tissue analysis showed region-specific expression changes in Wnt and NFAT signaling components. These effects were predominantly observed at the protein level in the striatum and cerebral cortex of LRRK2 KI mice. Primary neuronal cell culture analysis showed significant genotype-dependent alterations in Wnt and NFATc1 signaling under basal and stimulated conditions. Wnt and NFATc1 signaling was primarily dysregulated in cortical and hippocampal neurons respectively. Our study further built on knowledge of LRRK2 as a Wnt and NFAT signaling protein. We identified complex changes in neuronal models of LRRK2 PD, suggesting a role for mutant LRRK2 in the dysregulation of NFAT, and canonical and non-canonical Wnt signaling.
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Affiliation(s)
- Andrea Wetzel
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
- Institute of Physiology, Medical Faculty, Otto-von-Guericke-University, 39120, Magdeburg, Germany
| | - Si Hang Lei
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Tiansheng Liu
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Michael P Hughes
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Yunan Peng
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Tristan McKay
- Department of Life Sciences, Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK
| | - Simon N Waddington
- Gene Transfer Technology Group, University College London, 86-96 Chenies Mews, London, WC1E 6HXZ, UK
- Wits/SAMRC Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Simone Grannò
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
- Division of Neurosurgery, Department of Clinical Neurosciences, Geneva University Hospitals, Rue Gabrielle-Perret Gentil 4, 1205, Geneva, Switzerland
| | - Ahad A Rahim
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Kirsten Harvey
- Department of Pharmacology, UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
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Bow H, Dang C, Hillsbery K, Markowski C, Black M, Strand C. Food for Thought: The Effects of Feeding on Neurogenesis in the Ball Python, Python regius. BRAIN, BEHAVIOR AND EVOLUTION 2024; 99:144-157. [PMID: 38657588 DOI: 10.1159/000539052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Accepted: 04/16/2024] [Indexed: 04/26/2024]
Abstract
INTRODUCTION Pythons are a well-studied model of postprandial physiological plasticity. Consuming a meal evokes a suite of physiological changes in pythons including one of the largest documented increases in post-feeding metabolic rates relative to resting values. However, little is known about how this plasticity manifests in the brain. Previous work has shown that cell proliferation in the python brain increases 6 days following meal consumption. This study aimed to confirm these findings and build on them in the long term by tracking the survival and maturation of these newly created cells across a 2-month period. METHODS We investigated differences in neural cell proliferation in ball pythons 6 days after a meal with immunofluorescence using the cell-birth marker 5-bromo-12'-deoxyuridine (BrdU). We investigated differences in neural cell maturation in ball pythons 2 months after a meal using double immunofluorescence for BrdU and a reptilian ortholog of the neuronal marker Fox3. RESULTS We did not find significantly greater rates of cell proliferation in snakes 6 days after feeding, but we did observe more new cells in neurogenic regions in fed snakes 2 months after the meal. Feeding was not associated with higher rates of neurogenesis, but snakes that received a meal had higher numbers of newly created nonneuronal cells than fasted controls. We documented particularly high cell survival rates in the olfactory bulbs and lateral cortex. CONCLUSION Consuming a meal stimulates cell proliferation in the brains of ball pythons after digestion is complete, although this effect emerged at a later time point in this study than expected. Higher rates of proliferation partially account for greater numbers of newly created non-neuronal cells in the brains of fed snakes 2 months after the meal, but our results also suggest that feeding may have a mild neuroprotective effect. We captured a slight trend toward higher cell survival rates in fed snakes, and survival rates were particularly high in brain regions associated with olfactory perception and processing. These findings shed light on the relationship between energy balance and the creation of new neural cells in the brains of ball pythons.
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Affiliation(s)
- Hannah Bow
- Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California, USA
| | - Christina Dang
- Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California, USA
| | - Katherine Hillsbery
- Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California, USA
| | - Carly Markowski
- Biomedical Engineering Department, California Polytechnic State University, San Luis Obispo, California, USA
| | - Michael Black
- Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California, USA
| | - Christine Strand
- Biological Sciences Department, California Polytechnic State University, San Luis Obispo, California, USA
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Higuchi Y, Arakawa H. Serotonergic mediation of the brain-wide neurogenesis: Region-dependent and receptor-type specific roles on neurogenic cellular transformation. CURRENT RESEARCH IN NEUROBIOLOGY 2023; 5:100102. [PMID: 37638344 PMCID: PMC10458724 DOI: 10.1016/j.crneur.2023.100102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Revised: 06/18/2023] [Accepted: 07/15/2023] [Indexed: 08/29/2023] Open
Abstract
Brain serotonin (5-hydroxytryptamine, 5-HT) is a key molecule for the mediation of depression-related brain states, but the neural mechanisms underlying 5-HT mediation need further investigation. A possible mechanism of the therapeutic antidepressant effects is neurogenic cell production, as stimulated by 5-HT signaling. Neurogenesis, the proliferation of neural stem cells (NSCs), and cell differentiation and maturation occur across brain regions, particularly the hippocampal dentate gyrus and the subventricular zone, throughout one's lifespan. 5-HT plays a major role in the mediation of neurogenic processes, which in turn leads to the therapeutic effect on depression-related states. In this review article, we aim to identify how the neuronal 5-HT system mediates the process of neurogenesis, including cell proliferation, cell-type differentiation and maturation. First, we will provide an overview of the neurogenic cell transformation that occurs in brain regions containing or lacking NSCs. Second, we will review brain region-specific mechanisms of 5-HT-mediated neurogenesis by comparing regions localized to NSCs, i.e., the hippocampus and subventricular zone, with those not containing NSCs. Highlighting these 5-HT mechanisms that mediate neurogenic cell production processes in a brain-region-specific manner would provide unique insights into the role of 5-HT in neurogenesis and its associated effects on depression.
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Affiliation(s)
- Yuki Higuchi
- Department of Systems Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
| | - Hiroyuki Arakawa
- Department of Systems Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan
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Sex and Age-Dependent Olfactory Memory Dysfunction in ADHD Model Mice. Life (Basel) 2023; 13:life13030686. [PMID: 36983841 PMCID: PMC10056048 DOI: 10.3390/life13030686] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/23/2023] [Accepted: 03/01/2023] [Indexed: 03/06/2023] Open
Abstract
ADHD is a typical neurodevelopmental disorder with a high prevalence rate. NSCs in the subventricular zone (SVZ) are closely related to neurodevelopmental disorder and can affect olfactory function by neurogenesis and migratory route. Although olfactory dysfunction is one of the symptoms of ADHD, the relevance of cells in the olfactory bulb derived from NSCs has not been studied. Therefore, we investigated olfactory memory and NSCs in Git1-deficient mice, under the ADHD model. Interestingly, only adult male G protein-coupled receptor kinase-interacting protein-1 (GIT1)-deficient (+/−, HE) mice showed impaired olfactory memory, suggesting sex and age dependence. We performed adult NSCs culture from the SVZ and observed distinct cell population in both sex and genotype. Taken together, our study suggests that the altered differentiation of NSCs in GIT1+/− mice can contribute to olfactory dysfunction in ADHD.
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Butruille L, Sébillot A, Ávila K, Vancamp P, Demeneix BA, Pifferi F, Remaud S. Increased oligodendrogenesis and myelination in the subventricular zone of aged mice and gray mouse lemurs. Stem Cell Reports 2023; 18:534-554. [PMID: 36669492 PMCID: PMC9969077 DOI: 10.1016/j.stemcr.2022.12.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 12/16/2022] [Accepted: 12/20/2022] [Indexed: 01/20/2023] Open
Abstract
The adult rodent subventricular zone (SVZ) generates neural stem cells (NSCs) throughout life that migrate to the olfactory bulbs (OBs) and differentiate into olfactory interneurons. Few SVZ NSCs generate oligodendrocyte precursor cells (OPCs). We investigated how neurogliogenesis is regulated during aging in mice and in a non-human primate (NHP) model, the gray mouse lemur. In both species, neuronal commitment decreased with age, while OPC generation and myelin content unexpectedly increased. In the OBs, more tyrosine hydroxylase interneurons in old mice, but fewer in lemurs, marked a surprising interspecies difference that could relate to our observation of a continuous ventricle in lemurs. In the corpus callosum, aging promoted maturation of OPCs into mature oligodendrocytes in mice but blocked it in lemurs. The present study highlights similarities and dissimilarities between rodents and NHPs, revealing that NHPs are a more relevant model than mice to study the evolution of biomarkers of aging.
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Affiliation(s)
- Lucile Butruille
- Laboratory Molecular Physiology and Adaptation, CNRS UMR 7221, Department Adaptations of Life, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75005 Paris, France.
| | - Anthony Sébillot
- Laboratory Molecular Physiology and Adaptation, CNRS UMR 7221, Department Adaptations of Life, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75005 Paris, France
| | - Katia Ávila
- Laboratory Molecular Physiology and Adaptation, CNRS UMR 7221, Department Adaptations of Life, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75005 Paris, France
| | - Pieter Vancamp
- Laboratory Molecular Physiology and Adaptation, CNRS UMR 7221, Department Adaptations of Life, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75005 Paris, France
| | - Barbara A Demeneix
- Laboratory Molecular Physiology and Adaptation, CNRS UMR 7221, Department Adaptations of Life, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75005 Paris, France
| | - Fabien Pifferi
- UMR 7179 Mecadev, CNRS/Muséum National d'Histoire Naturelle, 1 Avenue du Petit Château, 91800 Brunoy, France
| | - Sylvie Remaud
- Laboratory Molecular Physiology and Adaptation, CNRS UMR 7221, Department Adaptations of Life, Muséum National d'Histoire Naturelle, 7 rue Cuvier, 75005 Paris, France.
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Role of Running-Activated Neural Stem Cells in the Anatomical and Functional Recovery after Traumatic Brain Injury in p21 Knock-Out Mice. Int J Mol Sci 2023; 24:ijms24032911. [PMID: 36769236 PMCID: PMC9918280 DOI: 10.3390/ijms24032911] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/28/2023] [Accepted: 01/30/2023] [Indexed: 02/05/2023] Open
Abstract
Traumatic brain injury (TBI) represents one of the most common worldwide causes of death and disability. Clinical and animal model studies have evidenced that TBI is characterized by the loss of both gray and white matter, resulting in brain atrophy and in a decrease in neurological function. Nowadays, no effective treatments to counteract TBI-induced neurological damage are available. Due to its complex and multifactorial pathophysiology (neuro-inflammation, cytotoxicity and astroglial scar formation), cell regeneration and survival in injured brain areas are strongly hampered. Recently, it has been proposed that adult neurogenesis may represent a new approach to counteract the post-traumatic neurodegeneration. In our laboratory, we have recently shown that physical exercise induces the long-lasting enhancement of subventricular (SVZ) adult neurogenesis in a p21 (negative regulator of neural progenitor proliferation)-null mice model, with a concomitant improvement of olfactory behavioral paradigms that are strictly dependent on SVZ neurogenesis. On the basis of this evidence, we have investigated the effect of running on SVZ neurogenesis and neurorepair processes in p21 knock-out mice that were subject to TBI at the end of a 12-day session of running. Our data indicate that runner p21 ko mice show an improvement in numerous post-trauma neuro-regenerative processes, including the following: (i) an increase in neuroblasts in the SVZ; (ii) an increase in the migration stream of new neurons from the SVZ to the damaged cortical region; (iii) an enhancement of new differentiating neurons in the peri-lesioned area; (iv) an improvement in functional recovery at various times following TBI. All together, these results suggest that a running-dependent increase in subventricular neural stem cells could represent a promising tool to improve the endogenous neuro-regenerative responses following brain trauma.
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Dunville K, Tonelli F, Novelli E, Codino A, Massa V, Frontino AM, Galfrè S, Biondi F, Gustincich S, Caleo M, Pandolfini L, Alia C, Cremisi F. Laminin 511 and WNT signalling sustain prolonged expansion of hiPSC-derived hippocampal progenitors. Development 2022; 149:276383. [DOI: 10.1242/dev.200353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 08/08/2022] [Indexed: 11/20/2022]
Abstract
ABSTRACT
Using the timely re-activation of WNT signalling in neuralizing human induced pluripotent stem cells (hiPSCs), we have produced neural progenitor cells with a gene expression profile typical of human embryonic dentate gyrus (DG) cells. Notably, in addition to continuous WNT signalling, a specific laminin isoform is crucial to prolonging the neural stem state and to extending progenitor cell proliferation for over 200 days in vitro. Laminin 511 is indeed specifically required to support proliferation and to inhibit differentiation of hippocampal progenitor cells for extended time periods when compared with a number of different laminin isoforms assayed. Global gene expression profiles of these cells suggest that a niche of laminin 511 and WNT signalling is sufficient to maintain their capability to undergo typical hippocampal neurogenesis. Moreover, laminin 511 signalling sustains the expression of a set of genes responsible for the maintenance of a hippocampal neurogenic niche. Finally, xenograft of human DG progenitors into the DG of adult immunosuppressed host mice produces efficient integration of neurons that innervate CA3 layer cells spanning the same area of endogenous hippocampal neuron synapses.
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Affiliation(s)
- Keagan Dunville
- Laboratorio di Biologia, Scuola Normale Superiore 1 , Pisa, 56126 , Italy
| | - Fabrizio Tonelli
- Laboratorio di Biologia, Scuola Normale Superiore 1 , Pisa, 56126 , Italy
| | - Elena Novelli
- Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche 2 , Pisa, 56124 , Italy
| | - Azzurra Codino
- Center for Human Technologies, Central RNA Lab, Istituto Italiano di Tecnologia 3 , Genova, 16152 , Italy
| | - Verediana Massa
- Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche 2 , Pisa, 56124 , Italy
| | | | - Silvia Galfrè
- Department of Biology and Biotechnologies ‘Charles Darwin’, Università La Sapienza 4 , Roma, 00185 , Italy
| | - Francesca Biondi
- Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche 2 , Pisa, 56124 , Italy
| | - Stefano Gustincich
- Center for Human Technologies, Central RNA Lab, Istituto Italiano di Tecnologia 3 , Genova, 16152 , Italy
| | - Matteo Caleo
- Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche 2 , Pisa, 56124 , Italy
| | - Luca Pandolfini
- Center for Human Technologies, Central RNA Lab, Istituto Italiano di Tecnologia 3 , Genova, 16152 , Italy
| | - Claudia Alia
- Istituto di Neuroscienze, Consiglio Nazionale delle Ricerche 2 , Pisa, 56124 , Italy
| | - Federico Cremisi
- Laboratorio di Biologia, Scuola Normale Superiore 1 , Pisa, 56126 , Italy
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12
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Expression of Transcription Factor ZBTB20 in the Adult Primate Neurogenic Niche under Physiological Conditions or after Ischemia. Genes (Basel) 2022; 13:genes13091559. [PMID: 36140727 PMCID: PMC9498320 DOI: 10.3390/genes13091559] [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: 07/02/2022] [Revised: 08/12/2022] [Accepted: 08/22/2022] [Indexed: 11/17/2022] Open
Abstract
The Zbtb20 gene encodes for a transcription factor that plays an important role in mammalian cortical development. Recently, its expression was reported in the adult mouse subventricular zone (SVZ), a major neurogenic niche containing neural stem cells throughout life. Here, we analyzed its expression in the adult primate anterior SVZ (SVZa) and rostral migratory stream (RMS) using macaque monkeys (Macaca fuscata). We report that the majority of Ki67+ cells, 71.4% in the SVZa and 85.7% in the RMS, co-label for ZBTB20. Nearly all neuroblasts, identified by their Doublecortin expression, were positive for ZBTB20 in both regions. Nearly all GFAP+ neural stem cells/astrocytes were also positive for ZBTB20. Analysis of images derived from a public database of gene expression in control/ischemic monkey SVZa, showed evidence for ZBTB20 upregulation in postischemic monkey SVZa. Furthermore, the co-localization of ZBTB20 with Doublecortin and Ki67 was increased in the postischemic SVZa. Our results suggest that ZBTB20 expression is evolutionarily conserved in the mammalian neurogenic niche and is reactive to ischemia. This opens the possibility for further functional studies on the role of this transcription factor in neurogenesis in primates.
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13
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Fabianová K, Babeľová J, Fabian D, Popovičová A, Martončíková M, Raček A, Račeková E. Maternal High-Energy Diet during Pregnancy and Lactation Impairs Neurogenesis and Alters the Behavior of Adult Offspring in a Phenotype-Dependent Manner. Int J Mol Sci 2022; 23:ijms23105564. [PMID: 35628378 PMCID: PMC9146615 DOI: 10.3390/ijms23105564] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 05/09/2022] [Accepted: 05/13/2022] [Indexed: 11/30/2022] Open
Abstract
Obesity is one of the biggest and most costly health challenges the modern world encounters. Substantial evidence suggests that the risk of metabolic syndrome or obesity formation may be affected at a very early stage of development, in particular through fetal and/or neonatal overfeeding. Outcomes from epidemiological studies indicate that maternal nutrition during pregnancy and lactation has a profound impact on adult neurogenesis in the offspring. In the present study, an intergenerational dietary model employing overfeeding of experimental mice during prenatal and early postnatal development was applied to acquire mice with various body conditions. We investigated the impact of the maternal high-energy diet during pregnancy and lactation on adult neurogenesis in the olfactory neurogenic region involving the subventricular zone (SVZ) and the rostral migratory stream (RMS) and some behavioral tasks including memory, anxiety and nociception. Our findings show that a maternal high-energy diet administered during pregnancy and lactation modifies proliferation and differentiation, and induced degeneration of cells in the SVZ/RMS of offspring, but only in mice where extreme phenotype, such as significant overweight/adiposity or obesity is manifested. Thereafter, a maternal high-energy diet enhances anxiety-related behavior in offspring regardless of its body condition and impairs learning and memory in offspring with an extreme phenotype.
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Affiliation(s)
- Kamila Fabianová
- Institute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Šoltésovej 4, 040 01 Košice, Slovakia; (A.P.); (M.M.); (A.R.); (E.R.)
- Correspondence:
| | - Janka Babeľová
- Centre of Biosciences, Institute of Animal Physiology, Slovak Academy of Sciences, Šoltésovej 4-6, 040 01 Košice, Slovakia; (J.B.); (D.F.)
| | - Dušan Fabian
- Centre of Biosciences, Institute of Animal Physiology, Slovak Academy of Sciences, Šoltésovej 4-6, 040 01 Košice, Slovakia; (J.B.); (D.F.)
| | - Alexandra Popovičová
- Institute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Šoltésovej 4, 040 01 Košice, Slovakia; (A.P.); (M.M.); (A.R.); (E.R.)
| | - Marcela Martončíková
- Institute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Šoltésovej 4, 040 01 Košice, Slovakia; (A.P.); (M.M.); (A.R.); (E.R.)
| | - Adam Raček
- Institute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Šoltésovej 4, 040 01 Košice, Slovakia; (A.P.); (M.M.); (A.R.); (E.R.)
| | - Enikő Račeková
- Institute of Neurobiology, Biomedical Research Center, Slovak Academy of Sciences, Šoltésovej 4, 040 01 Košice, Slovakia; (A.P.); (M.M.); (A.R.); (E.R.)
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14
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Hamdi H, Graiet I, Abid-Essefi S, Eyer J. Epoxiconazole profoundly alters rat brain and properties of neural stem cells. CHEMOSPHERE 2022; 288:132640. [PMID: 34695486 DOI: 10.1016/j.chemosphere.2021.132640] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 10/09/2021] [Accepted: 10/19/2021] [Indexed: 06/13/2023]
Abstract
Epoxiconazole (EPX), a widely used fungicide for domestic, medical, and industrial applications, could cause neurodegenerative diseases. However, the underling mechanism of neurotoxicity is not well understood. This study aimed to investigate the possible toxic outcomes of Epoxiconzole, a triazole fungicide, on the brain of adult rats in vivo, and in vitro on neural stem cells derived from the subventricular zone of newborn Wistar rats. Our results revealed that oral exposure to EPX at these concentrations (8, 24, 40, 56 mg/kg bw representing respectively NOEL (no observed effect level), NOEL × 3, NOEL × 5, and NOEL × 7) for 28 days caused a considerable generation of oxidative stress in adult rat brain tissue. Furthermore, a significant augmentation in lipid peroxidation and protein oxidation has been found. Moreover, it induced an elevation of DNA fragmentation as assessed by the Comet assay. Indeed, EPX administration impaired activities of antioxidant enzymes and inhibited AChE activity. Concomitantly, this pesticide produced histological alterations in the brain of adult rats. Regarding the embryonic neural stem cells, we demonstrated that the treatment by EPX reduced the viability of cells with an IC50 of 10 μM. It also provoked the reduction of cell proliferation, and EPX triggered arrest in G1/S phase. The neurosphere formation and self-renewal capacity was reduced and associated with decreased differentiation. Moreover, EPX induced cytoskeleton disruption as evidenced by immunocytochemical analysis. Our findings also showed that EPX induced apoptosis as evidenced by a loss of mitochondrial transmembrane potential (ΔΨm) and an activation of caspase-3. In addition, EPX promoted ROS production in neural stem cells. Interestingly, the pretreatment of neural stem cells with the N-acetylcysteine (ROS scavenger) attenuated EPX-induced cell death, disruption of neural stem cells properties, ROS generation and apoptosis. Thus, the use of this hazardous material should be restricted and carefully regulated.
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Affiliation(s)
- Hiba Hamdi
- Laboratory for Research on Biologically Compatible Compounds, Faculty of Dental Medicine, University of Monastir, Avicenne Street, 5019, Monastir, Tunisia; Higher Institute of Biotechnology, University of Monastir, Tunisia
| | - Imen Graiet
- Laboratory for Research on Biologically Compatible Compounds, Faculty of Dental Medicine, University of Monastir, Avicenne Street, 5019, Monastir, Tunisia
| | - Salwa Abid-Essefi
- Laboratory for Research on Biologically Compatible Compounds, Faculty of Dental Medicine, University of Monastir, Avicenne Street, 5019, Monastir, Tunisia
| | - Joel Eyer
- Laboratoire Micro et Nanomédecines Translationnelles (MINT), Inserm 1066, CNRS 6021, Institut de Biologie de La Santé, Centre Hospitalier Universitaire, 49033, Angers, France.
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15
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Martins-Macedo J, Salgado AJ, Gomes ED, Pinto L. Adult brain cytogenesis in the context of mood disorders: From neurogenesis to the emergent role of gliogenesis. Neurosci Biobehav Rev 2021; 131:411-428. [PMID: 34555383 DOI: 10.1016/j.neubiorev.2021.09.030] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 09/06/2021] [Accepted: 09/16/2021] [Indexed: 12/18/2022]
Abstract
Psychiatric disorders severely impact patients' lives. Motivational, cognitive and emotional deficits are the most common symptoms observed in these patients and no effective treatment is still available, either due to the adverse side effects or the low rate of efficacy of currently available drugs. Neurogenesis recovery has been one important focus in the treatment of psychiatric disorders, which undeniably contributes to the therapeutic action of antidepressants. However, glial plasticity is emerging as a new strategy to explore the deficits observed in mood disorders and the efficacy of therapeutic interventions. Thus, it is crucial to understand the mechanisms behind glio- and neurogenesis to better define treatments and preventive therapies, once adult cytogenesis is of pivotal importance to cognitive and emotional components of behavior, both in healthy and pathological contexts, including in psychiatric disorders. Here, we review the concepts and history of neuro- and gliogenesis, providing as well a reflection on the functional importance of cytogenesis in the context of disease.
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Affiliation(s)
- Joana Martins-Macedo
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - António J Salgado
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Eduardo D Gomes
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
| | - Luísa Pinto
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
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16
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Colussi C, Grassi C. Epigenetic regulation of neural stem cells: The emerging role of nucleoporins. STEM CELLS (DAYTON, OHIO) 2021; 39:1601-1614. [PMID: 34399020 PMCID: PMC9290943 DOI: 10.1002/stem.3444] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 07/28/2021] [Indexed: 11/06/2022]
Abstract
Nucleoporins (Nups) are components of the nuclear pore complex that, besides regulating nucleus-cytoplasmic transport, emerged as a hub for chromatin interaction and gene expression modulation. Specifically, Nups act in a dynamic manner both at specific gene level and in the topological organization of chromatin domains. As such, they play a fundamental role during development and determination of stemness/differentiation balance in stem cells. An increasing number of reports indicate the implication of Nups in many central nervous system functions with great impact on neurogenesis, neurophysiology, and neurological disorders. Nevertheless, the role of Nup-mediated epigenetic regulation in embryonic and adult neural stem cells (NSCs) is a field largely unexplored and the comprehension of their mechanisms of action is only beginning to be unveiled. After a brief overview of epigenetic mechanisms, we will present and discuss the emerging role of Nups as new effectors of neuroepigenetics and as dynamic platform for chromatin function with specific reference to the biology of NSCs.
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Affiliation(s)
- Claudia Colussi
- Istituto di Analisi dei Sistemi ed Informatica "Antonio Ruberti" (IASI)-CNR, Rome, Italy
| | - Claudio Grassi
- Department of Neuroscience, Università Cattolica del Sacro Cuore, Rome, Italy.,Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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17
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Brockman AA, Mobley BC, Ihrie RA. Histological Studies of the Ventricular-Subventricular Zone as Neural Stem Cell and Glioma Stem Cell Niche. J Histochem Cytochem 2021; 69:819-834. [PMID: 34310246 DOI: 10.1369/00221554211032003] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The neural stem cell niche of the ventricular-subventricular zone supports the persistence of stem and progenitor cells in the mature brain. This niche has many notable cytoarchitectural features that affect the activity of stem cells and may also support the survival and growth of invading tumor cells. Histochemical studies of the niche have revealed many proteins that, in combination, can help to reveal stem-like cells in the normal or cancer context, although many caveats persist in the quest to consistently identify these cells in the human brain. Here, we explore the complex relationship between the persistent proliferative capacity of the neural stem cell niche and the malignant proliferation of brain tumors, with a special focus on histochemical identification of stem cells and stem-like tumor cells and an eye toward the potential application of high-dimensional imaging approaches to the field.
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Affiliation(s)
- Asa A Brockman
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Bret C Mobley
- Departments of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Rebecca A Ihrie
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.,Departments of Neurological Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
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18
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Butruille L, Vancamp P, Demeneix BA, Remaud S. Thyroid hormone regulation of adult neural stem cell fate: A comparative analysis between rodents and primates. VITAMINS AND HORMONES 2021; 116:133-192. [PMID: 33752817 DOI: 10.1016/bs.vh.2021.02.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Thyroid hormone (TH) signaling, a highly conserved pathway across vertebrates, is crucial for brain development and function throughout life. In the adult mammalian brain, including that of humans, multipotent neural stem cells (NSCs) proliferate and generate neuronal and glial progenitors. The role of TH has been intensively investigated in the two main neurogenic niches of the adult mouse brain, the subventricular and the subgranular zone. A key finding is that T3, the biologically active form of THs, promotes NSC commitment toward a neuronal fate. In this review, we first discuss the roles of THs in the regulation of adult rodent neurogenesis, as well as how it relates to functional behavior, notably olfaction and cognition. Most research uncovering these roles of TH in adult neurogenesis was conducted in rodents, whose genetic background, brain structure and rate of neurogenesis are considerably different from that of humans. To bridge the phylogenetic gap, we also explore the similarities and divergences of TH-dependent adult neurogenesis in non-human primate models. Lastly, we examine how photoperiodic length changes TH homeostasis, and how that might affect adult neurogenesis in seasonal species to increase fitness. Several aspects by which TH acts on adult NSCs seem to be conserved among mammals, while we only start to uncover the molecular pathways, as well as how other in- and extrinsic factors are intertwined. A multispecies approach delivering more insights in the matter will pave the way for novel NSC-based therapies to combat neurological disorders.
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Affiliation(s)
- Lucile Butruille
- UMR 7221 Phyma, CNRS/Muséum National d'Histoire Naturelle, Paris, France
| | - Pieter Vancamp
- UMR 7221 Phyma, CNRS/Muséum National d'Histoire Naturelle, Paris, France
| | - Barbara A Demeneix
- UMR 7221 Phyma, CNRS/Muséum National d'Histoire Naturelle, Paris, France
| | - Sylvie Remaud
- UMR 7221 Phyma, CNRS/Muséum National d'Histoire Naturelle, Paris, France.
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19
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Jurkowski MP, Bettio L, K. Woo E, Patten A, Yau SY, Gil-Mohapel J. Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain. Front Cell Neurosci 2020; 14:576444. [PMID: 33132848 PMCID: PMC7550688 DOI: 10.3389/fncel.2020.576444] [Citation(s) in RCA: 133] [Impact Index Per Article: 26.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Accepted: 08/19/2020] [Indexed: 12/31/2022] Open
Abstract
Convincing evidence has repeatedly shown that new neurons are produced in the mammalian brain into adulthood. Adult neurogenesis has been best described in the hippocampus and the subventricular zone (SVZ), in which a series of distinct stages of neuronal development has been well characterized. However, more recently, new neurons have also been found in other brain regions of the adult mammalian brain, including the hypothalamus, striatum, substantia nigra, cortex, and amygdala. While some studies have suggested that these new neurons originate from endogenous stem cell pools located within these brain regions, others have shown the migration of neurons from the SVZ to these regions. Notably, it has been shown that the generation of new neurons in these brain regions is impacted by neurologic processes such as stroke/ischemia and neurodegenerative disorders. Furthermore, numerous factors such as neurotrophic support, pharmacologic interventions, environmental exposures, and stem cell therapy can modulate this endogenous process. While the presence and significance of adult neurogenesis in the human brain (and particularly outside of the classical neurogenic regions) is still an area of debate, this intrinsic neurogenic potential and its possible regulation through therapeutic measures present an exciting alternative for the treatment of several neurologic conditions. This review summarizes evidence in support of the classic and novel neurogenic zones present within the mammalian brain and discusses the functional significance of these new neurons as well as the factors that regulate their production. Finally, it also discusses the potential clinical applications of promoting neurogenesis outside of the classical neurogenic niches, particularly in the hypothalamus, cortex, striatum, substantia nigra, and amygdala.
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Affiliation(s)
- Michal P. Jurkowski
- Island Medical Program, University of British Columbia, Vancouver, BC, Canada
| | - Luis Bettio
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
| | - Emma K. Woo
- Island Medical Program, University of British Columbia, Vancouver, BC, Canada
| | - Anna Patten
- Centre for Interprofessional Clinical Simulation Learning (CICSL), Royal Jubilee Hospital, Victoria, BC, Canada
| | - Suk-Yu Yau
- Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hung Hom, Hong Kong
| | - Joana Gil-Mohapel
- Island Medical Program, University of British Columbia, Vancouver, BC, Canada
- Division of Medical Sciences, University of Victoria, Victoria, BC, Canada
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20
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Deboux C, Spigoni G, Caillava C, Garcia-Diaz B, Ypsilanti A, Sarrazin N, Bachelin C, Chédotal A, Baron-Van Evercooren A. Slit1 Protein Regulates SVZ-Derived Precursor Mobilization in the Adult Demyelinated CNS. Front Cell Neurosci 2020; 14:168. [PMID: 32670024 PMCID: PMC7332780 DOI: 10.3389/fncel.2020.00168] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Accepted: 05/19/2020] [Indexed: 01/03/2023] Open
Abstract
Slit1 is a secreted axon guidance molecule, also involved in adult neurogenesis. In physiological conditions, Slit1 loss promotes ectopic dispersal of SVZ-derived neural precursors (SVZ-NPCs) into periventricular structures such as the corpus callosum. Demyelination of the corpus callosum triggers SVZ-NPC migration to ectopic locations and their recruitment by the lesion, suggesting a possible role for Slit1 in SVZ-NPCs ectopic dispersal regulation in pathological conditions. Here, we have investigated the function of Slit1 protein in the recruitment of SVZ-NPCs after CNS demyelination. We find that the dynamics of oligodendrogenesis and temporal profile of developmental myelination in Slit1–/– mice are similar to Slit1+/− controls. SVZ micro-dissection and RT-PCR from wild-type mice, show that Slits and Robos are physiologically regulated at the transcriptional level in response to corpus callosum demyelination suggesting their role in the process of SVZ-NPC ectopic migration in demyelinating conditions. Moreover, we find that the number of SVZ-NPCs recruited by the lesion increases in Sli1–/– mice compared to Slit1+/− mice, leading to higher numbers of Olig2+ cells within the lesion. Time-lapse video-microscopy of immuno-purified NPCs shows that Slit1-deficient cells migrate faster and make more frequent directional changes than control NPCs, supporting a cell-autonomous mechanism of action of Slit1 in NPC migration. In conclusion, while Slit1 does not affect the normal developmental process of oligodendrogenesis and myelination, it regulates adult SVZ-NPC ectopic migration in response to demyelination, and consequently oligodendrocyte renewal within the lesion.
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Affiliation(s)
- C Deboux
- Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, France
| | - G Spigoni
- Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, France
| | - C Caillava
- Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, France
| | - B Garcia-Diaz
- Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, France
| | - A Ypsilanti
- Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
| | - N Sarrazin
- Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, France
| | - C Bachelin
- Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, France
| | - A Chédotal
- Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France
| | - A Baron-Van Evercooren
- Institut du Cerveau et de la Moelle épinière-Groupe Hospitalier Pitié-Salpêtrière, INSERM U1127, CNRS, UMR 7225, Sorbonne Université, UM75, Paris, France
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21
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Rossetti MF, Stoker C, Ramos JG. Agrochemicals and neurogenesis. Mol Cell Endocrinol 2020; 510:110820. [PMID: 32315720 DOI: 10.1016/j.mce.2020.110820] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 04/01/2020] [Accepted: 04/07/2020] [Indexed: 02/07/2023]
Abstract
Agrochemicals or pesticides are compounds widely used to prevent, destroy or mitigate pests such as insects, rodents, herbs and weeds. However, most of them also act as environmental estrogens, anti-estrogens and/or antiandrogenic chemicals. In addition, both herbicides (such as glyphosate and paraquat) and insecticides (such as pyrethroids, organophosphates, neonicotinoids and rotenone) have been shown to exert significant adverse effects on hippocampal neurogenesis. These effects are particularly important because neurogenesis dysregulation could be associated with cognitive decline and neuropathologies such as Alzheimer's disease. This review focuses on the most commonly used agrochemicals in Argentina and their effects on the hippocampal neurogenesis of mammals. It also discusses the disruption of hormone synthesis and action as a possible mechanism through which these chemical compounds could alter the brain functions. Finally, we propose some lines of research to study the potential endocrine mechanisms involved in the effects of agrochemicals on human health and biodiversity.
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Affiliation(s)
- M Florencia Rossetti
- Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Argentina; Instituto de Salud y Ambiente del Litoral (ISAL), Universidad Nacional del Litoral (UNL)- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Bioquímica y Ciencias Biológicas, UNL, Argentina
| | - Cora Stoker
- Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Argentina; Instituto de Salud y Ambiente del Litoral (ISAL), Universidad Nacional del Litoral (UNL)- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Bioquímica y Ciencias Biológicas, UNL, Argentina
| | - Jorge G Ramos
- Departamento de Bioquímica Clínica y Cuantitativa, Facultad de Bioquímica y Ciencias Biológicas, Universidad Nacional del Litoral, Argentina; Instituto de Salud y Ambiente del Litoral (ISAL), Universidad Nacional del Litoral (UNL)- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Bioquímica y Ciencias Biológicas, UNL, Argentina.
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22
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Akter M, Kaneko N, Sawamoto K. Neurogenesis and neuronal migration in the postnatal ventricular-subventricular zone: Similarities and dissimilarities between rodents and primates. Neurosci Res 2020; 167:64-69. [PMID: 32553727 DOI: 10.1016/j.neures.2020.06.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/22/2020] [Accepted: 06/04/2020] [Indexed: 12/26/2022]
Abstract
The ventricular-subventricular zone (V-SVZ) is located in the walls of the lateral ventricles and produces new neurons in the postnatal brain of mammals, including humans. Immature new neurons called "neuroblasts" generated by neural stem cells in the V-SVZ migrate toward their final destinations and contribute to brain development and plasticity. In this review, we describe recent progress in understanding the similarities and dissimilarities in postnatal neurogenesis and neuronal migration between rodents and primates. In rodents, most new V-SVZ-derived neurons migrate along the rostral migratory stream towards the olfactory bulb, where they differentiate into interneurons. In contrast, in humans, the extensive migration of new neurons towards the neocortex continues for several months after birth and might be involved in the development of the expanded neocortex. The mode of migration and the fate of neuroblasts seem to change depending on their environment, destination, and roles in the brain. A better understanding of these similarities and differences between rodents and primates will help translate important findings from animal models and may contribute to the development of clinical strategies for brain repair.
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Affiliation(s)
- Mariyam Akter
- Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan; Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Naoko Kaneko
- Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan; Division of Neural Development and Regeneration, National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi, 444-8787, Japan
| | - Kazunobu Sawamoto
- Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi, 467-8601, Japan; Division of Neural Development and Regeneration, National Institute for Physiological Sciences, National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki, Aichi, 444-8787, Japan.
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23
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Akter M, Kaneko N, Herranz-Pérez V, Nakamura S, Oishi H, García-Verdugo JM, Sawamoto K. Dynamic Changes in the Neurogenic Potential in the Ventricular-Subventricular Zone of Common Marmoset during Postnatal Brain Development. Cereb Cortex 2020; 30:4092-4109. [PMID: 32108222 DOI: 10.1093/cercor/bhaa031] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 01/07/2020] [Accepted: 01/26/2020] [Indexed: 12/15/2022] Open
Abstract
Even after birth, neuronal production continues in the ventricular-subventricular zone (V-SVZ) and hippocampus in many mammals. The immature new neurons ("neuroblasts") migrate and then mature at their final destination. In humans, neuroblast production and migration toward the neocortex and the olfactory bulb (OB) occur actively only for a few months after birth and then sharply decline with age. However, the precise spatiotemporal profiles and fates of postnatally born neurons remain unclear due to methodological limitations. We previously found that common marmosets, small nonhuman primates, share many features of V-SVZ organization with humans. Here, using marmosets injected with thymidine analogue(s) during various postnatal periods, we demonstrated spatiotemporal changes in neurogenesis during development. V-SVZ progenitor proliferation and neuroblast migration toward the OB and neocortex sharply decreased by 4 months, most strikingly in a V-SVZ subregion from which neuroblasts migrated toward the neocortex. Postnatally born neurons matured within a few months in the OB and hippocampus but remained immature until 6 months in the neocortex. While neurogenic activity was sustained for a month after birth, the distribution and/or differentiation diversity was more restricted in 1-month-born cells than in the neonatal-born population. These findings shed light on distinctive features of postnatal neurogenesis in primates.
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Affiliation(s)
- Mariyam Akter
- Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.,Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Naoko Kaneko
- Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.,Division of Neural Development and Regeneration, National Institute of Physiological Sciences, Okazaki 444-8787, Japan
| | - Vicente Herranz-Pérez
- Laboratory of Comparative Neurobiology, Instituto Cavanilles, Universidad de Valencia, 46980 Valencia, Spain.,Predepartmental Unit of Medicine, Faculty of Health Sciences, Universitat Jaume I, 12071 Castelló de la Plana, Spain
| | - Sayuri Nakamura
- Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
| | - Hisashi Oishi
- Department of Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
| | - Jose Manuel García-Verdugo
- Laboratory of Comparative Neurobiology, Instituto Cavanilles, Universidad de Valencia, 46980 Valencia, Spain
| | - Kazunobu Sawamoto
- Department of Developmental and Regenerative Neurobiology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan.,Division of Neural Development and Regeneration, National Institute of Physiological Sciences, Okazaki 444-8787, Japan
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24
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Lei S, Lu P, Lu Y, Zheng J, Li W, Wang N, Zhang H, Li R, Wang K, Wen J, Wei H, Zhang Y, Qiu Z, Xu J, Lv H, Chen X, Liu Y, Zhang P. Dexmedetomidine Alleviates Neurogenesis Damage Following Neonatal Midazolam Exposure in Rats through JNK and P38 MAPK Pathways. ACS Chem Neurosci 2020; 11:579-591. [PMID: 31999428 DOI: 10.1021/acschemneuro.9b00611] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Midazolam, a widely used anesthetic, inhibits proliferation of neural stem cells (NSCs) and induces neuroapoptosis in neonates. Dexmedetomidine, an effective auxiliary medicine in clinical anesthesia, protects the developing brain against volatile anesthetic-induced neuroapoptosis. Whether dexmedetomidine protects against neurogenesis damage induced by midazolam remains unknown. This study aims to clarify the protective effect of dexmedetomidine on midazolam-induced neurogenesis damage and explore its potential mechanism. Postnatal 7-day-old Sprague-Dawley (SD) rats and cultured NSCs were treated with either normal saline, midazolam, or dexmedetomidine combined with midazolam. The rats were sacrificed at 1, 3, and 7 days after treatment. Cell proliferation was assessed by 5-bromodeoxyurdine (BrdU) incorporation. Cell viability was determined using MTT assay. Cell differentiation and apoptosis were detected by immunofluorescent staining and terminal dUTP nick-end labeling (TUNEL), respectively. The protein levels of p-JNK, p-P38, and cleaved caspase-3 were quantified using Western blotting. Midazolam decreased cell proliferation and increased cell apoptosis in the subventricular zone (SVZ), the subgranular zone (SGZ) of the hippocampus, and cultured NSCs. Moreover, midazolam decreased cell viability and increased the expression of p-JNK and p-P38 in cultured NSCs. Co-treatment with dexmedetomidine attenuated midazolam-induced changes in cell proliferation, viability, apoptosis, and protein expression of p-JNK and p-P38 in cultured NSCs. Midazolam and dexmedetomidine did not affect the differentiation of the cultured NSCs. These results indicate that dexmedetomidine alleviated midazolam-induced neurogenesis damage via JNK and P38 MAPK pathways.
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Affiliation(s)
- Shan Lei
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Pan Lu
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Yang Lu
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Juan Zheng
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Weisong Li
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Ning Wang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Hong Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Rong Li
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Kui Wang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Jieqiong Wen
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Haidong Wei
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Yuanyuan Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Zhengguo Qiu
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Jing Xu
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Haixia Lv
- Institute of Neurobiology, National Key Academic Subject of Physiology of Xi’an Jiaotong University, Xi’an 710016, China
| | - Xinlin Chen
- Institute of Neurobiology, National Key Academic Subject of Physiology of Xi’an Jiaotong University, Xi’an 710016, China
| | - Yong Liu
- Institute of Neurobiology, National Key Academic Subject of Physiology of Xi’an Jiaotong University, Xi’an 710016, China
| | - Pengbo Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
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25
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Nakafuku M, Del Águila Á. Developmental dynamics of neurogenesis and gliogenesis in the postnatal mammalian brain in health and disease: Historical and future perspectives. WILEY INTERDISCIPLINARY REVIEWS-DEVELOPMENTAL BIOLOGY 2019; 9:e369. [PMID: 31825170 DOI: 10.1002/wdev.369] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 09/16/2019] [Accepted: 10/22/2019] [Indexed: 12/21/2022]
Abstract
The mature mammalian brain has long been thought to be a structurally rigid, static organ since the era of Ramón y Cajal in the early 20th century. Evidence accumulated over the past three decades, however, has completely overturned this long-held view. We now know that new neurons and glia are continuously added to the brain at postnatal stages, even in mature adults of various mammalian species, including humans. Moreover, these newly added cells contribute to structural plasticity and play important roles in higher order brain function, as well as repair after damage. A major source of these new neurons and glia is neural stem cells (NSCs) that persist in specialized niches in the brain throughout life. With this new view, our understanding of normal brain physiology and interventional approaches to various brain disorders has changed markedly in recent years. This article provides a brief overview on the historical changes in our understanding of the developmental dynamics of neurogenesis and gliogenesis in the postnatal and adult mammalian brain and discusses the roles of NSCs and other progenitor populations in such cellular dynamics in health and disease of the postnatal mammalian brain. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cells and Disease.
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Affiliation(s)
- Masato Nakafuku
- Divisions of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Ángela Del Águila
- Divisions of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
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26
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Current Progress of Research on Neurodegenerative Diseases of Salvianolic Acid B. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:3281260. [PMID: 31341529 PMCID: PMC6612994 DOI: 10.1155/2019/3281260] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 05/29/2019] [Indexed: 12/30/2022]
Abstract
Salvia miltiorrhiza Bunge (Lamiaceae), one of the most commonly used traditional Chinese herbs, is widely used for the treatment of cardiovascular disease, cerebrovascular disease, Alzheimer's disease, and Parkinson's disease in clinical practice. Salvianolic acid B (Sal B, C36H30O16, FW = 718.62) is the main water-soluble active ingredient of Salvia miltiorrhiza Bunge, which performs prophylactic and therapeutic activities against neurodegenerative diseases. So far, numerous studies have proved that multiple factors and mechanisms are involved in the pathological process of neurodegenerative diseases, including amyloid β (Aβ) aggregation and fibril formation, hyperphosphorylation of tau protein, neuroinflammation, oxidative-stress damage, mitochondrial dysfunction, and neuron apoptosis. This study is aimed at reviewing experimental studies and describing the possible mechanisms of Sal B on neurodegenerative diseases.
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27
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Nemirovich-Danchenko NM, Khodanovich MY. New Neurons in the Post-ischemic and Injured Brain: Migrating or Resident? Front Neurosci 2019; 13:588. [PMID: 31275097 PMCID: PMC6591486 DOI: 10.3389/fnins.2019.00588] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 05/23/2019] [Indexed: 12/11/2022] Open
Abstract
The endogenous potential of adult neurogenesis is of particular interest for the development of new strategies for recovery after stroke and traumatic brain injury. These pathological conditions affect endogenous neurogenesis in two aspects. On the one hand, injury usually initiates the migration of neuronal precursors (NPCs) to the lesion area from the already existing, in physiological conditions, neurogenic niche - the ventricular-subventricular zone (V-SVZ) near the lateral ventricles. On the other hand, recent studies have convincingly demonstrated the local generation of new neurons near lesion areas in different brain locations. The striatum, cortex, and hippocampal CA1 region are considered to be locations of such new neurogenic zones in the damaged brain. This review focuses on the relative contribution of two types of NPCs of different origin, resident population in new neurogenic zones and cells migrating from the lateral ventricles, to post-stroke or post-traumatic enhancement of neurogenesis. The migratory pathways of NPCs have also been considered. In addition, the review highlights the advantages and limitations of different methodological approaches to the definition of NPC location and tracking of new neurons. In general, we suggest that despite the considerable number of studies, we still lack a comprehensive understanding of neurogenesis in the damaged brain. We believe that the advancement of methods for in vivo visualization and longitudinal observation of neurogenesis in the brain could fundamentally change the current situation in this field.
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Affiliation(s)
| | - Marina Yu. Khodanovich
- Laboratory of Neurobiology, Research Institute of Biology and Biophysics, Tomsk State University, Tomsk, Russia
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28
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Iwamura H, Kondo K, Kikuta S, Nishijima H, Kagoya R, Suzukawa K, Ando M, Fujimoto C, Toma-Hirano M, Yamasoba T. Caloric restriction reduces basal cell proliferation and results in the deterioration of neuroepithelial regeneration following olfactotoxic mucosal damage in mouse olfactory mucosa. Cell Tissue Res 2019; 378:175-193. [PMID: 31168693 DOI: 10.1007/s00441-019-03047-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 05/10/2019] [Indexed: 01/18/2023]
Abstract
The effects of caloric restriction (CR) on cell dynamics and gene expression in the mouse olfactory neuroepithelium are evaluated. Eight-week-old male C57BL/6 mice were fed either control pellets (104 kcal/week) or CR pellets (67 kcal/week). The cytoarchitecture of the olfactory neuroepithelium in the uninjured condition and its regeneration after injury by an olfactotoxic chemical, methimazole, were compared between mice fed with the control and CR diets. In the uninjured condition, there were significantly fewer olfactory marker protein (OMP)-positive olfactory receptor neurons and Ki67-positive proliferating basal cells at 3 months in the CR group than in the control group. The number of Ki67-positive basal cells increased after methimazole-induced mucosal injury in both the control and the CR groups, but the increase was less robust in the CR group. The recovery of the neuroepithelium at 2 months after methimazole administration was less complete in the CR group than in the control group. These histological changes were region-specific. The decrease in the OMP-positive neurons was prominent in the anterior region of the olfactory mucosa. Gene expression analysis using a DNA microarray and quantitative real-time polymerase chain reaction demonstrated that the expression levels of two inflammatory cytokines, interleukin-6 and chemokine ligand 1, were elevated in the olfactory mucosa of the CR group compared with the control group. These findings suggest that CR may be disadvantageous to the maintenance of the olfactory neuroepithelium, especially when it is injured.
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Affiliation(s)
- Hitoshi Iwamura
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Kenji Kondo
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Shu Kikuta
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Hironobu Nishijima
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Ryoji Kagoya
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Keigo Suzukawa
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Mizuo Ando
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Chisato Fujimoto
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Makiko Toma-Hirano
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
| | - Tatsuya Yamasoba
- Department of Otolaryngology-Head and Neck Surgery, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan
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29
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Mason DM, Wang Y, Bhatia TN, Miner KM, Trbojevic SA, Stolz JF, Luk KC, Leak RK. The center of olfactory bulb-seeded α-synucleinopathy is the limbic system and the ensuing pathology is higher in male than in female mice. Brain Pathol 2019; 29:741-770. [PMID: 30854742 DOI: 10.1111/bpa.12718] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 03/03/2019] [Indexed: 12/18/2022] Open
Abstract
At early disease stages, Lewy body disorders are characterized by limbic vs. brainstem α-synucleinopathy, but most preclinical studies have focused solely on the nigrostriatal pathway. Furthermore, male gender and advanced age are two major risk factors for this family of conditions, but their influence on the topographical extents of α-synucleinopathy and the degree of cell loss are uncertain. To fill these gaps, we infused α-synuclein fibrils in the olfactory bulb/anterior olfactory nucleus complex-one of the earliest and most frequently affected brain regions in Lewy body disorders-in 3-month-old female and male mice and in 11-month-old male mice. After 6 months, we observed that α-synucleinopathy did not expand significantly beyond the limbic connectome in the 9-month-old male and female mice or in the 17-month-old male mice. However, the 9-month-old male mice had developed greater α-synucleinopathy, smell impairment and cell loss than age-matched females. By 10.5 months post-infusion, fibril treatment hastened mortality in the 21.5-month-old males, but the inclusions remained centered in the limbic system in the survivors. Although fibril infusions reduced the number of cells expressing tyrosine hydroxylase in the substantia nigra of young males at 6 months post-infusion, this was not attributable to true cell death. Furthermore, mesencephalic α-synucleinopathy, if present, was centered in mesolimbic circuits (ventral tegmental area/accumbens) rather than within strict boundaries of the nigral pars compacta, which were defined here by tyrosine hydroxylase immunolabel. Nonprimate models cannot be expected to faithfully recapitulate human Lewy body disorders, but our murine model seems reasonably suited to (i) capture some aspects of Stage IIb of Lewy body disorders, which displays a heavier limbic than brainstem component compared to incipient Parkinson's disease; and (ii) leverage sex differences and the acceleration of mortality following induction of olfactory α-synucleinopathy.
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Affiliation(s)
- Daniel M Mason
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA
| | - Yaqin Wang
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA
| | - Tarun N Bhatia
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA
| | - Kristin M Miner
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA
| | - Sara A Trbojevic
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA
| | - John F Stolz
- Department of Biological Sciences, Duquesne University, Pittsburgh, PA
| | - Kelvin C Luk
- Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Rehana K Leak
- Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA
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30
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Rodrigues RS, Lourenço DM, Paulo SL, Mateus JM, Ferreira MF, Mouro FM, Moreira JB, Ribeiro FF, Sebastião AM, Xapelli S. Cannabinoid Actions on Neural Stem Cells: Implications for Pathophysiology. Molecules 2019; 24:E1350. [PMID: 30959794 PMCID: PMC6480122 DOI: 10.3390/molecules24071350] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/01/2019] [Accepted: 04/03/2019] [Indexed: 02/06/2023] Open
Abstract
With the increase of life expectancy, neurodegenerative disorders are becoming not only a health but also a social burden worldwide. However, due to the multitude of pathophysiological disease states, current treatments fail to meet the desired outcomes. Therefore, there is a need for new therapeutic strategies focusing on more integrated, personalized and effective approaches. The prospect of using neural stem cells (NSC) as regenerative therapies is very promising, however several issues still need to be addressed. In particular, the potential actions of pharmacological agents used to modulate NSC activity are highly relevant. With the ongoing discussion of cannabinoid usage for medical purposes and reports drawing attention to the effects of cannabinoids on NSC regulation, there is an enormous, and yet, uncovered potential for cannabinoids as treatment options for several neurological disorders, specifically when combined with stem cell therapy. In this manuscript, we review in detail how cannabinoids act as potent regulators of NSC biology and their potential to modulate several neurogenic features in the context of pathophysiology.
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Affiliation(s)
- Rui S Rodrigues
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Diogo M Lourenço
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Sara L Paulo
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Joana M Mateus
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Miguel F Ferreira
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Francisco M Mouro
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - João B Moreira
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Filipa F Ribeiro
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Ana M Sebastião
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
| | - Sara Xapelli
- Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, 1649-028 Lisboa, Portugal.
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31
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Kostin A, Alam MA, McGinty D, Szymusiak R, Alam MN. Chronic Suppression of Hypothalamic Cell Proliferation and Neurogenesis Induces Aging-Like Changes in Sleep–Wake Organization in Young Mice. Neuroscience 2019; 404:541-556. [DOI: 10.1016/j.neuroscience.2019.01.053] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 12/14/2018] [Accepted: 01/28/2019] [Indexed: 10/27/2022]
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The Role of SVZ Stem Cells in Glioblastoma. Cancers (Basel) 2019; 11:cancers11040448. [PMID: 30934929 PMCID: PMC6521108 DOI: 10.3390/cancers11040448] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 03/22/2019] [Accepted: 03/26/2019] [Indexed: 12/27/2022] Open
Abstract
As most common primary brain cancer, glioblastoma is also the most aggressive and malignant form of cancer in the adult central nervous system. Glioblastomas are genetic and transcriptional heterogeneous tumors, which in spite of intensive research are poorly understood. Over the years conventional therapies failed to affect a cure, resulting in low survival rates of affected patients. To improve the clinical outcome, an important approach is to identify the cells of origin. One potential source for these are neural stem cells (NSCs) located in the subventricular zone, which is one of two niches in the adult nervous system where NSCs with the capacity of self-renewal and proliferation reside. These cells normally give rise to neuronal as well as glial progenitor cells. This review summarizes current findings about links between NSCs and cancer stem cells in glioblastoma and discusses current therapeutic approaches, which arise as a result of identifying the cell of origin in glioblastoma.
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33
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Huang Z, Wang Y. In Vivo Electroporation and Time-Lapse Imaging of the Rostral Migratory Stream in Developing Rodent Brain. ACTA ACUST UNITED AC 2019; 87:e65. [PMID: 30861320 DOI: 10.1002/cpns.65] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Interneurons in the olfactory bulb are generated from neuronal precursor cells migrating from the anterior subventricular zone (SVZa) throughout the embryonic and postnatal life of mammals. This article describes basic methods for in vivo electroporation to label SVZa cells of both embryonic and postnatal rats. In addition, it describes three methods for tracing SVZa progenitors and following their migration pathway and differentiation, including immunohistochemistry, time-lapse live imaging in slice culture, and time-lapse imaging following transplantation in slice culture. These methods may be applied to all strains of rats and mice, including reporter mice. They may also be combined with methods such as BrdU labeling, tamoxifen injection, and electrophysiology, allowing one to observe proliferation or control gene expression at specific times and for specific neuronal functions. With time-lapse live imaging, details of labeled cells can be studied, including morphology, motility pattern, differentiation, and crosstalk between cells. © 2019 by John Wiley & Sons, Inc.
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Affiliation(s)
- Zhihui Huang
- Institute of Neuroscience, Wenzhou Medical College, Wenzhou, Zhejiang, China
| | - Ying Wang
- Institute of Clinical Research, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.,Department of Blood Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China
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Cannabinoid signalling in embryonic and adult neurogenesis: possible implications for psychiatric and neurological disorders. Acta Neuropsychiatr 2019; 31:1-16. [PMID: 29764526 DOI: 10.1017/neu.2018.11] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Cannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods. The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions. Studies reporting participation of cannabinoids on the regulation of any step of neurogenesis and the effects of cannabinoid compounds on animal models possessing neurogenesis-dependent features were selected from Medline. Qualitative evaluation of the selected studies indicated that activation of cannabinoid receptors may change neurogenesis in embryonic or adult nervous systems alongside rescue of phenotypes in animal models of different psychiatric and neurological disorders. The text offers an overview on the effects of cannabinoids on central nervous system development and the possible links with psychiatric and neurological disorders such as anxiety, depression, schizophrenia, brain ischaemia/stroke and Alzheimer's disease. An understanding of the mechanisms by which cannabinoid signalling influences developmental and adult neurogenesis will help foster the development of new therapeutic strategies for neurodevelopmental, psychiatric and neurological disorders.
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Chandwani MN, Creisher PS, O'Donnell LA. Understanding the Role of Antiviral Cytokines and Chemokines on Neural Stem/Progenitor Cell Activity and Survival. Viral Immunol 2018; 32:15-24. [PMID: 30307795 DOI: 10.1089/vim.2018.0091] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Viral infections of the central nervous system are accompanied by the expression of cytokines and chemokines that can be critical for the control of viral replication in the brain. The outcomes of cytokine/chemokine signaling in neural cells vary widely, with cell-specific effects on cellular activity, proliferation, and survival. Neural stem/progenitor cells (NSPCs) are often altered during viral infections, through direct infection by the virus or by the influence of immune cell activity or cytokine/chemokine signaling. However, it has been challenging to dissect the contribution of the virus and specific inflammatory mediators during an infection. In addition to initiating an antiviral program in infected NSPCs, cytokines/chemokines can induce multiple changes in NSPC behavior that can perturb NSPC numbers, differentiation into other neural cells, and migration to sites of injury, and ultimately brain development and repair. The focus of this review was to dissect the effects of common antiviral cytokines and chemokines on NSPC activity, and to consider the subsequent pathological consequences for the host from changes in NSPC function.
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Affiliation(s)
- Manisha N Chandwani
- Department of Pharmaceutical, Administrative, and Social Sciences, Graduate School of Pharmaceutical Sciences, Duquesne University School of Pharmacy , Pittsburgh, Pennsylvania
| | - Patrick S Creisher
- Department of Pharmaceutical, Administrative, and Social Sciences, Graduate School of Pharmaceutical Sciences, Duquesne University School of Pharmacy , Pittsburgh, Pennsylvania
| | - Lauren A O'Donnell
- Department of Pharmaceutical, Administrative, and Social Sciences, Graduate School of Pharmaceutical Sciences, Duquesne University School of Pharmacy , Pittsburgh, Pennsylvania
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36
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Hussain R, Zubair H, Pursell S, Shahab M. Neurodegenerative Diseases: Regenerative Mechanisms and Novel Therapeutic Approaches. Brain Sci 2018; 8:E177. [PMID: 30223579 PMCID: PMC6162719 DOI: 10.3390/brainsci8090177] [Citation(s) in RCA: 139] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Revised: 09/03/2018] [Accepted: 09/12/2018] [Indexed: 12/12/2022] Open
Abstract
Regeneration refers to regrowth of tissue in the central nervous system. It includes generation of new neurons, glia, myelin, and synapses, as well as the regaining of essential functions: sensory, motor, emotional and cognitive abilities. Unfortunately, regeneration within the nervous system is very slow compared to other body systems. This relative slowness is attributed to increased vulnerability to irreversible cellular insults and the loss of function due to the very long lifespan of neurons, the stretch of cells and cytoplasm over several dozens of inches throughout the body, insufficiency of the tissue-level waste removal system, and minimal neural cell proliferation/self-renewal capacity. In this context, the current review summarized the most common features of major neurodegenerative disorders; their causes and consequences and proposed novel therapeutic approaches.
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Affiliation(s)
- Rashad Hussain
- Center for Translational Neuromedicine, University of Rochester, NY 14642, USA.
| | - Hira Zubair
- Department of Animal Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
| | - Sarah Pursell
- Center for Translational Neuromedicine, University of Rochester, NY 14642, USA.
| | - Muhammad Shahab
- Department of Animal Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
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37
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Orechio D, Andrade Aguiar B, Baroni Diniz G, Cioni Bittencourt J, Haemmerle CAS, Watanabe IS, Miglino MA, Castelucci P. Morphological and Cellular Characterization of the Fetal Canine (Canis lupus familiaris) Subventricular Zone, Rostral Migratory Stream, and Olfactory Bulb. Anat Rec (Hoboken) 2018; 301:1570-1584. [PMID: 29752870 DOI: 10.1002/ar.23855] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2017] [Revised: 01/22/2018] [Accepted: 01/30/2018] [Indexed: 01/06/2023]
Abstract
The existence of neurogenesis in the adult brain is a widely recognized phenomenon, occurring in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone of the dentate gyrus in several vertebrate species. Neural precursors originated in the SVZ migrate to the main olfactory bulb (MOB), originating the rostral migratory stream (RMS) in the process. To better understand the formation of the adult neurogenic niches in dogs, we investigated the cellular composition and morphological organization of these areas in 57 days-old dog fetuses. Using multiple immunohistochemical markers, we demonstrated that the SVZ in the canine fetus is remarkably similar to the adult SVZ, with glial GFAP-immunoreactive (-ir) cells, DCX-ir neuroblasts and SOX2-ir neuronal progenitors tangentially organized along the dorsal lateral ventricle. The fetal RMS has all the features of its adult counterpart and closely resembles the RMS of other mammalian species. The late-development canine MOB has most of the neurochemical features of the adult MOB, including an early-developed TH-ir population and maturing CALR-ir interneurons, but CALB-ir neurons in the granule cell layer will only appear in the post-partum period. Taken together, our results suggest that the canine fetal development of adult neurogenic niches closely resembles those of primates, and dogs may be suitable models of human adult neurogenesis. Anat Rec, 301:1570-1584, 2018. © 2018 Wiley Periodicals, Inc.
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Affiliation(s)
- Dailiany Orechio
- Department of Surgery, Faculty of Veterinary Medicine and Zootechny, University of São Paulo, São Paulo, Brazil
| | - Bruna Andrade Aguiar
- Department of Surgery, Faculty of Veterinary Medicine and Zootechny, University of São Paulo, São Paulo, Brazil
| | - Giovanne Baroni Diniz
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | | | - Carlos A S Haemmerle
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.,Department of Anatomy, Sector of Biological Sciences, Federal University of Paraná, Curitiba, Brazil
| | - Ii-Sei Watanabe
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Maria Angelica Miglino
- Department of Surgery, Faculty of Veterinary Medicine and Zootechny, University of São Paulo, São Paulo, Brazil
| | - Patricia Castelucci
- Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
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38
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Xie YW, Li ZY, Du J, Chen Y, Chen BY, Wang TT, Huang Z, Hou S, Wang Y. Visualization of Rostral Migratory Stream in the Developing Rat Brain by In Vivo Electroporation. Cell Mol Neurobiol 2018; 38:1067-1079. [PMID: 29441488 PMCID: PMC11481847 DOI: 10.1007/s10571-018-0577-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2017] [Accepted: 02/06/2018] [Indexed: 12/11/2022]
Abstract
Interneurons in the olfactory bulb (OB) are generated from neuronal precursor cells migrating from anterior subventricular zone (SVZa) not only in the developing embryo but also throughout the postnatal life of mammals. In the present study, we established an in vivo electroporation assay to label SVZa cells of rat both at embryonic and postnatal ages, and traced SVZa progenitors and followed their migration pathway and differentiation. We found that labeled cells displayed high motility. Interestingly, the postnatal cells migrated faster than the embryonic cells after applying this assay at different ages of brain development. Furthermore, based on brain slice culture and time-lapse imaging, we analyzed the detail migratory properties of these labeled precursor neurons. Finally, tissue transplantation experiments revealed that cells already migrated in subependymal zone of OB were transplanted back into rostral migratory stream (RMS), and these cells could still migrate out tangentially along RMS to OB. Taken together, these findings provide an in vivo labeling assay to follow and trace migrating cells in the RMS, their maturation and integration into OB neuron network, and unrecognized phenomena that postnatal SVZa progenitor cells with higher motility than embryonic cells, and their migration was affected by extrinsic environments.
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Affiliation(s)
- Yi-Wei Xie
- Department of Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China
| | - Zhao-Yun Li
- Department of Clinical Laboratory, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, 318000, Zhejiang, China
| | - Jing Du
- Department of Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China
| | - Yu Chen
- Department of Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China
| | - Bing-Yu Chen
- Department of Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China
| | - Tong-Tong Wang
- Department of Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China
| | - Zhihui Huang
- Wenzhou Medical University, Institute of Neuroscience, Wenzhou, 325035, Zhejiang, China.
| | - Shuangxing Hou
- Department of Neurology, ShanghaiPudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Pudong, 201399, Shanghai, China.
| | - Ying Wang
- Department of Transfusion, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, China.
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39
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van der Ven AT, Pape JC, Hermann D, Schloesser R, Genius J, Fischer N, Mößner R, Scherbaum N, Wiltfang J, Rujescu D, Benninghoff J. Methylene Blue (Tetramethylthionine Chloride) Influences the Mobility of Adult Neural Stem Cells: A Potentially Novel Therapeutic Mechanism of a Therapeutic Approach in the Treatment of Alzheimer's Disease. J Alzheimers Dis 2018; 57:531-540. [PMID: 28269766 DOI: 10.3233/jad-160755] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
An interest in neurogenesis in the adult human brain as a relevant and targetable process has emerged as a potential treatment option for Alzheimer's disease and other neurodegenerative conditions. The aim of this study was to investigate the effects of tetramethylthionine chloride (methylene blue, MB) on properties of adult murine neural stem cells. Based on recent clinical studies, MB has increasingly been discussed as a potential treatment for Alzheimer's disease. While no differences in the proliferative capacity were identified, a general potential of MB in modulating the migratory capacity of adult neural stem cells was indicated in a cell mobility assay. To our knowledge, this is the first time that MB could be associated with neural mobility. The results of this study add insight to the spectrum of features of MB within the central nervous system and may be helpful for understanding the molecular mechanisms underlying a potential therapeutic effect of MB.
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Affiliation(s)
- Amelie T van der Ven
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, LVR Hospital, Essen, Germany.,Department of Medicine, Division of Nephrology, Boston Children's Hospital, Harvard Medical School, MA, USA
| | | | - Dirk Hermann
- Department of Neurology, Chair of Vascular Neurology and Dementia, University Hospital of Essen, Germany
| | | | - Just Genius
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, LVR Hospital, Essen, Germany
| | - Nadine Fischer
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, LVR Hospital, Essen, Germany
| | - Rainald Mößner
- Department of Psychiatry, University of Tübingen, Germany
| | - Norbert Scherbaum
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, LVR Hospital, Essen, Germany
| | - Jens Wiltfang
- Department of Psychiatry, University of Göttingen, Germany
| | - Dan Rujescu
- Department of Psychiatry and Psychotherapy, University of Halle (Saale), Germany
| | - Jens Benninghoff
- Department of Psychiatry and Psychotherapy, Faculty of Medicine, University of Duisburg-Essen, LVR Hospital, Essen, Germany
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40
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Seki K, Yoshida S, Jaiswal MK. Molecular mechanism of noradrenaline during the stress-induced major depressive disorder. Neural Regen Res 2018; 13:1159-1169. [PMID: 30028316 PMCID: PMC6065220 DOI: 10.4103/1673-5374.235019] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Chronic stress-induced depression is a common hallmark of many psychiatric disorders with high morbidity rate. Stress-induced dysregulation of noradrenergic system has been implicated in the pathogenesis of depression. Lack of monoamine in the brain has been believed to be the main causative factor behind pathophysiology of major depressive disorder (MDD) and several antidepressants functions by increasing the monoamine level at the synapses in the brain. However, it is undetermined whether the noradrenergic receptor stimulation is critical for the therapeutic effect of antidepressant. Contrary to noradrenergic receptor stimulation, it has been suggested that the desensitization of β-adrenoceptor is involved in the therapeutic effect of antidepressant. In addition, enhanced noradrenaline (NA) release is central response to stress and thought to be a risk factor for the development of MDD. Moreover, fast acting antidepressant suppresses the hyperactivation of noradrenergic neurons in locus coeruleus (LC). However, it is unclear how they alter the firing activity of LC neurons. These inconsistent reports about antidepressant effect of NA-reuptake inhibitors (NRIs) and enhanced release of NA as a stress response complicate our understanding about the pathophysiology of MDD. In this review, we will discuss the role of NA in pathophysiology of stress and the mechanism of therapeutic effect of NA in MDD. We will also discuss the possible contributions of each subtype of noradrenergic receptors on LC neurons, hypothalamic-pituitary-adrenal axis (HPA-axis) and brain derived neurotrophic factor-induced hippocampal neurogenesis during stress and therapeutic effect of NRIs in MDD.
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Affiliation(s)
- Kenjiro Seki
- Department of Pharmacology, School of Pharmaceutical Science, Ohu University, Fukushima, Japan
| | - Satomi Yoshida
- Department of Pharmacology, School of Pharmaceutical Science, Ohu University, Fukushima, Japan
| | - Manoj Kumar Jaiswal
- Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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41
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Gothié JD, Demeneix B, Remaud S. Comparative approaches to understanding thyroid hormone regulation of neurogenesis. Mol Cell Endocrinol 2017; 459:104-115. [PMID: 28545819 DOI: 10.1016/j.mce.2017.05.020] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 05/11/2017] [Accepted: 05/19/2017] [Indexed: 12/12/2022]
Abstract
Thyroid hormone (TH) signalling, an evolutionary conserved pathway, is crucial for brain function and cognition throughout life, from early development to ageing. In humans, TH deficiency during pregnancy alters offspring brain development, increasing the risk of cognitive disorders. How TH regulates neurogenesis and subsequent behaviour and cognitive functions remains a major research challenge. Cellular and molecular mechanisms underlying TH signalling on proliferation, survival, determination, migration, differentiation and maturation have been studied in mammalian animal models for over a century. However, recent data show that THs also influence embryonic and adult neurogenesis throughout vertebrates (from mammals to teleosts). These latest observations raise the question of how TH availability is controlled during neurogenesis and particularly in specific neural stem cell populations. This review deals with the role of TH in regulating neurogenesis in the developing and the adult brain across different vertebrate species. Such evo-devo approaches can shed new light on (i) the evolution of the nervous system and (ii) the evolutionary control of neurogenesis by TH across animal phyla. We also discuss the role of thyroid disruptors on brain development in an evolutionary context.
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Affiliation(s)
- Jean-David Gothié
- CNRS, UMR 7221, Muséum National d'Histoire Naturelle, F-75005 Paris France
| | - Barbara Demeneix
- CNRS, UMR 7221, Muséum National d'Histoire Naturelle, F-75005 Paris France.
| | - Sylvie Remaud
- CNRS, UMR 7221, Muséum National d'Histoire Naturelle, F-75005 Paris France.
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42
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43
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García-González D, Khodosevich K, Watanabe Y, Rollenhagen A, Lübke JHR, Monyer H. Serotonergic Projections Govern Postnatal Neuroblast Migration. Neuron 2017; 94:534-549.e9. [PMID: 28472655 DOI: 10.1016/j.neuron.2017.04.013] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 03/08/2017] [Accepted: 04/05/2017] [Indexed: 01/18/2023]
Abstract
In many vertebrates, postnatally generated neurons often migrate long distances to reach their final destination, where they help shape local circuit activity. Concerted action of extrinsic stimuli is required to regulate long-distance migration. Some migratory principles are evolutionarily conserved, whereas others are species and cell type specific. Here we identified a serotonergic mechanism that governs migration of postnatally generated neurons in the mouse brain. Serotonergic axons originating from the raphe nuclei exhibit a conspicuous alignment with subventricular zone-derived neuroblasts. Optogenetic axonal activation provides functional evidence for serotonergic modulation of neuroblast migration. Furthermore, we show that the underlying mechanism involves serotonin receptor 3A (5HT3A)-mediated calcium influx. Thus, 5HT3A receptor deletion in neuroblasts impaired speed and directionality of migration and abolished calcium spikes. We speculate that serotonergic modulation of postnatally generated neuroblast migration is evolutionarily conserved as indicated by the presence of serotonergic axons in migratory paths in other vertebrates.
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Affiliation(s)
- Diego García-González
- Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Konstantin Khodosevich
- Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200 Copenhagen, Denmark
| | - Yasuhito Watanabe
- Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Astrid Rollenhagen
- Institute of Neuroscience and Medicine INM-2, Research Centre Jülich GmbH, Leo-Brandt Str., 52425 Jülich, Germany
| | - Joachim H R Lübke
- Institute of Neuroscience and Medicine INM-2, Research Centre Jülich GmbH, Leo-Brandt Str., 52425 Jülich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH/University Hospital Aachen, Pauwelstr. 30, 52074 Aachen, Germany; JARA Translational Brain Medicine, Jülich and Aachen, Germany
| | - Hannah Monyer
- Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
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Anand SK, Mondal AC. Cellular and molecular attributes of neural stem cell niches in adult zebrafish brain. Dev Neurobiol 2017; 77:1188-1205. [PMID: 28589616 DOI: 10.1002/dneu.22508] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Revised: 04/05/2017] [Accepted: 06/02/2017] [Indexed: 12/20/2022]
Abstract
Adult neurogenesis is a complex, presumably conserved phenomenon in vertebrates with a broad range of variations regarding neural progenitor/stem cell niches, cellular composition of these niches, migratory patterns of progenitors and so forth among different species. Current understanding of the reasons underlying the inter-species differences in adult neurogenic potential, the identification and characterization of various neural progenitors, characterization of the permissive environment of neural stem cell niches and other important aspects of adult neurogenesis is insufficient. In the last decade, zebrafish has emerged as a very useful model for addressing these questions. In this review, we have discussed the present knowledge regarding the neural stem cell niches in adult zebrafish brain as well as their cellular and molecular attributes. We have also highlighted their similarities and differences with other vertebrate species. In the end, we shed light on some of the known intrinsic and extrinsic factors that are assumed to regulate the neurogenic process in adult zebrafish brain. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1188-1205, 2017.
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Affiliation(s)
- Surendra Kumar Anand
- Cellular and Molecular Neurobiology Lab, School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, India, 110067
| | - Amal Chandra Mondal
- Cellular and Molecular Neurobiology Lab, School of Life Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, India, 110067
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45
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Exfoliated Human Olfactory Neuroepithelium: A Source of Neural Progenitor Cells. Mol Neurobiol 2017; 55:2516-2523. [PMID: 28391555 DOI: 10.1007/s12035-017-0500-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2017] [Accepted: 03/16/2017] [Indexed: 10/19/2022]
Abstract
Neural progenitor cells (NPC) contained in the human adult olfactory neuroepithelium (ONE) possess an undifferentiated state, the capability of self-renewal, the ability to generate neural and glial cells as well as being kept as neurospheres in cell culture conditions. Recently, NPC have been isolated from human or animal models using high-risk surgical methods. Therefore, it was necessary to improve methodologies to obtain and maintain human NPC as well as to achieve better knowledge of brain disorders. In this study, we propose the establishment and characterization of NPC cultures derived from the human olfactory neuroepithelium, using non-invasive procedures. Twenty-two healthy individuals (29.7 ± 4.5 years of age) were subjected to nasal exfoliation. Cells were recovered and kept as neurospheres under serum-free conditions. The neural progenitor origin of these neurospheres was determined by immunocytochemistry and qPCR. Their ability for self-renewal and multipotency was analyzed by clonogenic and differentiation assays, respectively. In the cultures, the ONE cells preserved the phenotype of the neurospheres. The expression levels of Nestin, Musashi, Sox2, and βIII-tubulin demonstrated the neural origin of the neurospheres; 48% of the cells separated could generate neurospheres, determining that they retained their self-renewal capacity. Neurospheres were differentiated in the absence of growth factors (EGF and FGF), and their multipotency ability was maintained as well. We were also able to isolate and grow human neural progenitor cells (neurospheres) through nasal exfoliates (non-invasive method) of the ONE from healthy adults, which is an extremely important contribution for the study of brain disorders and for the development of new therapies.
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PM 2.5 Exposure Suppresses Dendritic Maturation in Subgranular Zone in Aged Rats. Neurotox Res 2017; 32:50-57. [PMID: 28275902 PMCID: PMC5487878 DOI: 10.1007/s12640-017-9710-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 02/03/2017] [Accepted: 02/13/2017] [Indexed: 01/19/2023]
Abstract
Detrimental effects of long-term inhalation of fine particulate matter (PM2.5) on the pulmonary and cardiovascular systems have been widely reported. Recent studies have shown that exposure to PM2.5 also causes adverse neurocognitive effects. This study investigates the effects of inhaled ammonium sulfate, which is a major compound of inorganic air pollutants in PM2.5, on adult neurogenesis in aged Sprague-Dawley rats. A total of 20 rats were randomly assigned to experimental (n = 10) and control (n = 10) conditions, wherein they were exposed to either ammonium sulfate or sham air for 2 h per day and for 28 consecutive days. It was observed that ammonium sulfate inhibited the maturation process and diminished dendritic complexity of immature neurons in the subgranular zone (SGZ) of the hippocampus significantly, although the number of neural stem cells or the rates of differentiation were comparable between the two groups. Our findings provide clear evidence on the direct relationship between air quality and advantageous neurogenesis. Exposure to PM leads to specific adverse effects on the maturation process during neurogenesis.
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Injection of SDF-1 loaded nanoparticles following traumatic brain injury stimulates neural stem cell recruitment. Int J Pharm 2017; 519:323-331. [DOI: 10.1016/j.ijpharm.2017.01.036] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Revised: 01/16/2017] [Accepted: 01/17/2017] [Indexed: 01/05/2023]
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de Lucia C, Murphy T, Thuret S. Emerging Molecular Pathways Governing Dietary Regulation of Neural Stem Cells during Aging. Front Physiol 2017; 8:17. [PMID: 28194114 PMCID: PMC5276856 DOI: 10.3389/fphys.2017.00017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Accepted: 01/09/2017] [Indexed: 12/22/2022] Open
Abstract
Aging alters cellular and molecular processes, including those of stem cells biology. In particular, changes in neural stem cells (NSCs) are linked to cognitive decline associated with aging. Recently, the systemic environment has been shown to alter both NSCs regulation and age-related cognitive decline. Interestingly, a well-documented and naturally occurring way of altering the composition of the systemic environment is through diet and nutrition. Furthermore, it is well established that the presence of specific nutrients as well as the overall increase or reduction of calorie intake can modulate conserved molecular pathways and respectively reduce or increase lifespan. In this review, we examine these pathways in relation to their function on NSCs and cognitive aging. We highlight the importance of the Sirtuin, mTOR and Insulin/Insulin like growth factor-1 pathways as well as the significant role played by epigenetics in the dietary regulation of NSCs and the need for further research to exploit nutrition as a mode of intervention to regulate NSCs aging.
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Affiliation(s)
| | | | - Sandrine Thuret
- Neurogenesis and Mental Health Laboratory, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College LondonLondon, UK
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Prenatal Alcohol Exposure Affects Progenitor Cell Numbers in Olfactory Bulbs and Dentate Gyrus of Vervet Monkeys. Brain Sci 2016; 6:brainsci6040052. [PMID: 27801790 PMCID: PMC5187566 DOI: 10.3390/brainsci6040052] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 10/21/2016] [Accepted: 10/23/2016] [Indexed: 01/18/2023] Open
Abstract
Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts vervet monkey (Chlorocebus sabeus) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group. These data are unique with respect to fetal ethanol effects on progenitor proliferation in the primate brain and suggest that the olfactory bulb may be a useful structure for studies of cellular proliferation.
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50
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Chang EH, Adorjan I, Mundim MV, Sun B, Dizon MLV, Szele FG. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche. Front Neurosci 2016; 10:332. [PMID: 27531972 PMCID: PMC4969304 DOI: 10.3389/fnins.2016.00332] [Citation(s) in RCA: 69] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 06/30/2016] [Indexed: 01/07/2023] Open
Abstract
Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI.
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Affiliation(s)
- Eun Hyuk Chang
- Samsung Biomedical Research Institute, Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd. Seoul, South Korea
| | - Istvan Adorjan
- Department of Physiology, Anatomy and Genetics, University of OxfordOxford, UK; Department of Anatomy, Histology and Embryology, Semmelweis UniversityBudapest, Hungary
| | - Mayara V Mundim
- Department of Biochemistry, Universidade Federal de São Paulo São Paulo, Brazil
| | - Bin Sun
- Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, UK
| | - Maria L V Dizon
- Department of Pediatrics, Prentice Women's Hospital, Northwestern University Feinberg School of Medicine Chicago, IL, USA
| | - Francis G Szele
- Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, UK
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