scholarly journals Adult hypothalamic neurogenesis and sleep–wake dysfunction in aging

SLEEP ◽  
2020 ◽  
Author(s):  
Andrey Kostin ◽  
Md Aftab Alam ◽  
Dennis McGinty ◽  
Md Noor Alam
Keyword(s):  
Ventricular Zone ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Mammalian Brain ◽  
Hypothalamic Area ◽  
Age Related ◽  
Pharmacological Stimulation ◽  
Stem And Progenitor Cells ◽  
The Face ◽  
Regulatory Challenges

Abstract In the mammalian brain, adult neurogenesis has been extensively studied in the hippocampal sub-granular zone and the sub-ventricular zone of the anterolateral ventricles. However, growing evidence suggests that new cells are not only “born” constitutively in the adult hypothalamus, but many of these cells also differentiate into neurons and glia and serve specific functions. The preoptic-hypothalamic area plays a central role in the regulation of many critical functions, including sleep–wakefulness and circadian rhythms. While a role for adult hippocampal neurogenesis in regulating hippocampus-dependent functions, including cognition, has been extensively studied, adult hypothalamic neurogenic process and its contributions to various hypothalamic functions, including sleep–wake regulation are just beginning to unravel. This review is aimed at providing the current understanding of the hypothalamic adult neurogenic processes and the extent to which it affects hypothalamic functions, including sleep–wake regulation. We propose that hypothalamic neurogenic processes are vital for maintaining the proper functioning of the hypothalamic sleep–wake and circadian systems in the face of regulatory challenges. Sleep–wake disturbance is a frequent and challenging problem of aging and age-related neurodegenerative diseases. Aging is also associated with a decline in the neurogenic process. We discuss a hypothesis that a decrease in the hypothalamic neurogenic process underlies the aging of its sleep–wake and circadian systems and associated sleep–wake disturbance. We further discuss whether neuro-regenerative approaches, including pharmacological and non-pharmacological stimulation of endogenous neural stem and progenitor cells in hypothalamic neurogenic niches, can be used for mitigating sleep–wake and other hypothalamic dysfunctions in aging.

scholarly journals Telomere length and human hippocampal neurogenesis

2020 ◽  
Vol 45 (13) ◽  
pp. 2239-2247 ◽  
Author(s):  
Alish B. Palmos ◽  
Rodrigo R. R. Duarte ◽  
Demelza M. Smeeth ◽  
Erin C. Hedges ◽  
Douglas F. Nixon ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Psychiatric Disorder ◽  
Telomere Length ◽  
Gene Networks ◽  
Hippocampal Neurogenesis ◽  
Telomere Maintenance ◽  
Adult Hippocampal Neurogenesis ◽  
Telomere Shortening ◽  
Age Related

Abstract Short telomere length is a risk factor for age-related disease, but it is also associated with reduced hippocampal volumes, age-related cognitive decline and psychiatric disorder risk. The current study explored whether telomere shortening might have an influence on cognitive function and psychiatric disorder pathophysiology, via its hypothesised effects on adult hippocampal neurogenesis. We modelled telomere shortening in human hippocampal progenitor cells in vitro using a serial passaging protocol that mimics the end-replication problem. Serially passaged progenitors demonstrated shorter telomeres (P ≤ 0.05), and reduced rates of cell proliferation (P ≤ 0.001), with no changes in the ability of cells to differentiate into neurons or glia. RNA-sequencing and gene-set enrichment analyses revealed an effect of cell ageing on gene networks related to neurogenesis, telomere maintenance, cell senescence and cytokine production. Downregulated transcripts in our model showed a significant overlap with genes regulating cognitive function (P ≤ 1 × 10−5), and risk for schizophrenia (P ≤ 1 × 10−10) and bipolar disorder (P ≤ 0.005). Collectively, our results suggest that telomere shortening could represent a mechanism that moderates the proliferative capacity of human hippocampal progenitors, which may subsequently impact on human cognitive function and psychiatric disorder pathophysiology.

scholarly journals The pharmacological stimulation of Nurr1 improves cognitive functions via enhancement of adult hippocampal neurogenesis

2016 ◽  
Vol 17 (3) ◽  
pp. 534-543 ◽  
Author(s):  
Jin-il Kim ◽  
Seong Gak Jeon ◽  
Kyoung Ah Kim ◽  
Yong Jun Kim ◽  
Eun Ji Song ◽  
...  
Keyword(s):  
Cognitive Functions ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Pharmacological Stimulation ◽  
Stimulation Of

Early age-related changes in adult hippocampal neurogenesis in C57 mice

2010 ◽  
Vol 31 (1) ◽  
pp. 151-161 ◽  
Author(s):  
Nada M.-B. Ben Abdallah ◽  
Lutz Slomianka ◽  
Alexei L. Vyssotski ◽  
Hans-Peter Lipp
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Early Age ◽  
Age Related ◽  
Age Related Changes

scholarly journals Shaping hippocampal neurogenesis: exercising the brain with cannabinoids

2020 ◽  
Author(s):  
Rui S Rodrigues ◽  
Joao B. Moreira ◽  
Ana M. Sebastião ◽  
Carlos P. Fitzsimons ◽  
Sara Xapelli
Keyword(s):  
Physical Exercise ◽  
Progenitor Cells ◽  
Neurotrophic Factors ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Fine Tuning ◽  
Mammalian Brain ◽  
Potential Conflict ◽  
Brain Physiology ◽  
The Brain

Adult neural stem/progenitor cells (NSPC) are present in specialized niches of the mammalian brain and their proliferative and differentiative potential is modulated by a myriad of factors. Recent evidence sheds light on the interaction between cannabinoids and neurotrophic factors underlying a major regulative force of adult hippocampal neurogenesis, with important effects upon cognitive plasticity and mood flexibility. Herein, we aimed at evaluating the actions of cannabinoid type 2 receptor (CB2R) together with exercise upon hippocampal neurogenesis and whether this has significant behavioral implications. Our data suggests a participation of CB2Rs in fine-tuning the actions of physical exercise upon adult hippocampal neurogenesis. Specifically, CB2R ligands as well as exercise-regulated neurotrophic factors promote an acceleration in the differentiation of progenitor cells accompanied by an increase in the number of mature neurons in vitro. Moreover, preliminary results show that CB2Rs play an impactful role in controlling cognitive and depressive-like behavior. This is particularly important because brain physiology and mental health are known to be greatly affected by physical exercise, with adult neurogenesis playing a significant role in this process. Ultimately, this work will contribute to unravel the mechanisms behind the actions of cannabinoids and exercise in the brain and to develop strategies utilizing CB2Rs and physical exercise to boost neural stem cell capacity and treat several brain disorders. Acknowledgements: Supported by Fundação para a Ciência e a Tecnologia (FCT), projects SFRH/BD/129710/2017 and IF/01227/2015. No potential conflict of interest.

scholarly journals Oleic acid triggers hippocampal neurogenesis by binding to TLX/NR2E1

2020 ◽  
Author(s):  
Prasanna Kandel ◽  
Fatih Semerci ◽  
Aleksandar Bajic ◽  
Dodge Baluya ◽  
LiHua Ma ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Oleic Acid ◽  
Progenitor Cell ◽  
Monounsaturated Fatty Acids ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Orphan Nuclear Receptor ◽  
Endogenous Ligand ◽  
Self Renewal ◽  
Stem And Progenitor Cells

AbstractAdult hippocampal neurogenesis underpins learning, memory, and mood, but diminishes with age and illness. The orphan nuclear receptor TLX/NR2E1 is known to regulate neural stem and progenitor cell self-renewal and proliferation, but the precise mechanism by which it accomplishes this is unknown. We found that neural stem and progenitor cells require monounsaturated fatty acids to survive and proliferate. Specifically, oleic acid (18:1ω9) binds to TLX to convert it from a transcriptional repressor to a transcriptional activator of cell cycle and neurogenesis genes. We propose a model in which sufficient quantities of this endogenous ligand must bind to TLX to trigger the switch to proliferation. These findings pave the way for future therapeutic manipulations to counteract pathogenic impairments of neurogenesis.

scholarly journals Adult hippocampal neurogenesis of mammals: evolution and life history

2008 ◽  
Vol 5 (1) ◽  
pp. 141-144 ◽  
Author(s):  
Irmgard Amrein ◽  
Hans-Peter Lipp
Keyword(s):  
Hippocampal Formation ◽  
Mammalian Species ◽  
Critical Role ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Mammalian Brain ◽  
Spatial Learning And Memory ◽  
Species Specific ◽  
Species Being

Substantial production of new neurons in the adult mammalian brain is restricted to the olfactory system and the hippocampal formation. Its physiological and behavioural role is still debated. By comparing adult hippocampal neurogenesis (AHN) across many mammalian species, one might recognize a common function. AHN is most prominent in rodents, but shows considerable variability across species, being lowest or missing in primates and bats. The latter finding argues against a critical role of AHN in spatial learning and memory. The common functional denominator across all species investigated thus far is a strong decline of AHN from infancy to midlife. As predicted by Altman and colleagues in 1973, this implies a role in transforming juvenile unpredictable to predictable behaviour, typically characterizing mammalian behaviour once reproductive competence has been attained. However, as only a fraction of mammalian species has been investigated, further comparative studies are necessary in order to recognize whether AHN has a common unique function, or whether it mediates species-specific hippocampal functions.

scholarly journals Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Zocher ◽  
Rupert W. Overall ◽  
Mathias Lesche ◽  
Andreas Dahl ◽  
Gerd Kempermann
Keyword(s):  
Dna Methylation ◽  
Brain Function ◽  
Environmental Enrichment ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Aged Mouse ◽  
Lifestyle Interventions ◽  
Epigenetic Changes ◽  
Aging Effects ◽  
Age Related

AbstractThe decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.

scholarly journals Vangl2, a core component of the WNT/PCP pathway, regulates adult hippocampal neurogenesis and age-related decline in cognitive flexibility

2021 ◽  
Author(s):  
M Koehl ◽  
E Ladevèze ◽  
M Montcouquiol ◽  
DN Abrous
Keyword(s):  
Episodic Memory ◽  
Dentate Gyrus ◽  
Cognitive Flexibility ◽  
Adult Neurogenesis ◽  
Continuous Production ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Core Component ◽  
Dominant Negative Mutation ◽  
Age Related

AbstractDecline in episodic memory is one of the hallmarks of aging and represents one of the most important health problems facing western societies. A key structure in episodic memory is the hippocampal formation and the dentate gyrus in particular, as the continuous production of new dentate granule neurons in this brain region was found to play a crucial role in memory and in age-related decline in memory. As such, understanding the molecular processes that regulate the relationship between adult neurogenesis and aging of memory function holds great therapeutic potential. Recently, we found that Vang-gogh like 2 (Vangl2), a core component of the planar cell polarity signaling pathway, is enriched in the dentate gyrus of adult mice. In this context, we sought to evaluate the involvement of this effector of the Wnt/PCP pathway in both adult neurogenesis and memory abilities in adult and middle-aged mice. Using a heterozygous mouse model carrying a dominant negative mutation in Vangl2 gene, we show that alteration in Vangl2 expression decreases the survival of adult-born granule cells and advances the onset of decrease in cognitive flexibility. Inability of mutant mice to erase old irrelevant information to the benefit of new relevant ones highlights a key role of Vangl2 in interference-based forgetting. Taken together, our findings show for the first that Vangl2 activity may constitute an interesting target to prevent age-related decline in hippocampal plasticity and memory.

scholarly journals Age-related decline in BubR1 impairs adult hippocampal neurogenesis

Aging Cell ◽  
2017 ◽  
Vol 16 (3) ◽  
pp. 598-601 ◽  
Author(s):  
Zhongxi Yang ◽  
Heechul Jun ◽  
Chan-II Choi ◽  
Ki Hyun Yoo ◽  
Chang Hoon Cho ◽  
...  
Keyword(s):  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Age Related

Amyloid beta induced Neurotoxicity Impairs Cognition and Adult hippocampal Neurogenesis in a Mouse Model for Alzheimer’s disease

2020 ◽  
Vol 17 ◽  
Author(s):  
Sanila Amber ◽  
Phdabs Sumera ◽  
Fatima Javed Mirza ◽  
Muhammad Asif ◽  
Deeba Hassan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Beta ◽  
Substantial Reduction ◽  
Treatment Strategies ◽  
Conclusive Evidence ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Mammalian Brain

Background: Neurogenesis, the key mechanism to generate new neurons from existing stem cell niches continues throughout the life in the adult mammalian brain, although decelerate with aging or the progression of neurodegenerative disorders like Alzheimer’s disease (AD). In the past few years, impaired adult hippocampal neurogenesis emerged as a contributing hallmark of AD pathophysiology along with amyloid beta (Aβ) and tau hyper phosphorylationinduced neurotoxicity. However, no conclusive evidence exists that indicates the up/down-regulation of adult hippocampal neurogenesis during the course of AD progression. Methodology: In this study, we examined alterations in adult hippocampal neurogenesis and cognitive deficits using Aβ (1- 42)-induced mouse model of AD. Results: Our results demonstrate that Aβ administration induces an anxiety like behavior and impairs spatial and non-spatial memory and learning in BALB/c mice. Extensive neuronal loss was also evident in the dentate gyrus (DG), CA1, CA2 and CA3 regions of hippocampus in Aβ-treated animals. Furthermore, Aβ-exposure markedly reduced the real-time expression of markers of cell proliferation and migration i.e. Ki67 and DCX, whereas immunohistochemistry analysis revealed a substantial reduction in the expression levels of Ki67 and NeuN. Conclusion: Our findings highlight the association of Aβ-induced neurotoxicity with altered neurogenesis and memory formation; however further insight is warranted to explore the underlying molecular pathway(s). Moreover, the treatment strategies aiming to repair the adult hippocampal neurogenesis hold potential as AD therapeutics.

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