Concise Review: Regulatory Influence of Sleep and Epigenetics on Adult Hippocampal Neurogenesis and Cognitive and Emotional Function

Abstract

Neural stem and progenitor cells continue to generate new neurons in particular regions of the brain during adulthood. One of these neurogenic regions is the dentate gyrus (DG) of the hippocampus, which plays an important role in cognition and emotion. By exploiting this innate neuronal regeneration mechanism in the DG, new technologies have the potential to promote resistance to or recovery from brain dysfunction or degeneration. However, a deeper understanding of how adult DG neurogenesis is regulated by factors such as sleep and epigenetic modifications of gene expression could lead to further breakthroughs in the clinical application of neural stem and progenitor cells. In this review, we discuss the functions of adult-born DG neurons, describe the epigenetic regulation of adult DG neurogenesis, identify overlaps in how sleep and epigenetic modifications impact adult DG neurogenesis and memory consolidation, and suggest ways of using sleep or epigenetic interventions as therapies for neurodegenerative and psychiatric disorders. By knitting together separate strands of the literature, we hope to trigger new insights into how the functions of adult-generated neurons are directed by interactions between sleep-related neural processes and epigenetic mechanisms to facilitate novel approaches to preventing and treating brain disorders such as depression, post-traumatic stress disorder, and Alzheimer's disease. STEM CELLS 2018; 00:000-000 SIGNIFICANCE STATEMENTNew technologies utilizing neural stem cells in the adult hippocampus could potentially be used to promote innate resistance to or recovery from brain dysfunction or degeneration. Accumulating evidence indicates that adult hippocampal neurogenesis contributes to cognitive and emotional processing and is regulated by sleep and epigenetic modification of gene expression. Therefore, a richer understanding of how the interplay between sleep and epigenetics impacts adult hippocampal neurogenesis and thereby influences hippocampal function can help advance efforts to employ behavioral sleep interventions, epigenetic drugs, and novel neural stem cell-based therapeutic strategies for preventing or treating neurodegenerative and psychiatric disorders.

The bidirectional causal relationships of insomnia with five major psychiatric disorders: A Mendelian randomization study

“…Charrier and collaborators highlighted that SNPs in core circadian clock genes are associated with psychiatric disorders [11]. Additionally, Akers and colleagues evaluated the regulation of sleep and epigenetic modifications on adult neurogenesis and memory consolidation, and suggested ways of using sleep as therapy for psychiatric disorders [12]. However, despite these findings, the underlying cause-effect relationships are not clearly established.…”

Effects of Huazhuo Jiedu Shugan Decoction on Cognitive and Emotional Disorders in a Rat Model of Epilepsy: Possible Involvement of AC-cAMP-CREB Signaling and NPY Expression

“…Hippocampus is the best area to observe the pharmacodynamic changes in cognitive and emotional disorders caused by epileptic injury [39,40]. e occurrence of epilepsy is closely related to the hippocampus and CA1, CA3, and DG, as important regions of the hippocampus, are important areas of epilepsy research [41][42][43].…”

A within‐subject consideration of the psychotic spectrum disorder concept in a patient in remission associated with cortical gray matter recovery

“…Gamma oscillations are particularly prominent during nonrapid eye movement (non-REM) sleep and are important for integration of information across distant brain regions involved in memory consolidation. 37 It is also of interest that neurogenesis has been linked to sleep (Akers et al 2018) since recovery from psychosis was achieve while the patient was asleep. 38 Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and various neuregulins are likely to be key to the regrowth of neuropil or neurogenesis.…”

“…37 It is also of interest that neurogenesis has been linked to sleep (Akers et al 2018) since recovery from psychosis was achieve while the patient was asleep. 38 Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and various neuregulins are likely to be key to the regrowth of neuropil or neurogenesis. 39,40 Both of these neurotrophins have been shown to be stimulated by atypical APDs, as well as many other mechanisms.…”