Epigenetics, hippocampal neurogenesis, and neuropsychiatric disorders: Unraveling the genome to understand the mind
Open accessAbstract
In mature, differentiated neurons in the central nervous system (CNS), epigenetic mechanisms--including DNA methylation, histone modification, and regulatory noncoding RNAs--play critical roles in encoding experience and environmental stimuli into stable, behaviorally meaningful changes in gene expression. For example, epigenetic changes in mature hippocampal neurons have been implicated in learning and memory and in a variety of neuropsychiatric disorders, including depression. With all the recent (and warranted) attention given to epigenetic modifications in mature neurons, it is easy to forget that epigenetic mechanisms were initially described for their ability to promote differentiation and drive cell fate in embryonic and early postnatal development, including neurogenesis. Given the discovery of ongoing neurogenesis in the adult brain and the intriguing links among adult hippocampal neurogenesis, hippocampal function, and neuropsychiatric disorders, it is timely to complement the ongoing discussions on the role of epigenetics in mature neurons with a review on what is currently known about the role of epigenetics in adult hippocampal neurogenesis. The process of adult hippocampal neurogenesis is complex, with neural stem cells (NSCs) giving rise to fate-restricted progenitors and eventually mature dentate gyrus granule cells. Notably, neurogenesis occurs within an increasingly well-defined "neurogenic niche", where mature cellular elements like vasculature, astrocytes, and neurons release signals that can dynamically regulate neurogenesis. Here we review the evidence that key stages and aspects of adult neurogenesis are driven by epigenetic mechanisms. We discuss the intrinsic changes occurring within NSCs and their progeny that are critical for neurogenesis. We also discuss how extrinsic changes occurring in cellular components in the niche can result in altered neurogenesis. Finally we describe the potential relevance of epigenetics for understanding the relationship between hippocampal neurogenesis in neuropsychiatric disorders. We propose that a more thorough understanding of the molecular and genetic mechanisms that control the complex process of neurogenesis, including the proliferation and differentiation of NSCs, will lead to novel therapeutics for the treatment of neuropsychiatric disorders.
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Epigenetic mechanisms include modifications in response to environmental stimuli, and contribute to cell- and tissue-specific gene expression profiles during brain development involving processes such as neurogenesis and synaptic plasticity.
“Epigenetic mechanisms include modifications in response to environmental stimuli, and contribute to cell- and tissue-specific gene expression profiles during brain development involving processes such as neurogenesis and synaptic plasticity 14, 15.”
From Resilience in mental health: linking psychological and neurobiological perspectives. (2013) · cites this paper as [14]
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The Transcription Regulator Patz1 Is Essential for Neural Stem Cell Maintenance and Proliferation
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Homocysteine levels impact directly on epigenetic reprogramming in astrocytes
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Epigenetic Regulation of the Hippocampus, with Special Reference to Radiation Exposure
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- Authors
- Hsieh, J., & Eisch, A. J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Hsieh, Jenny
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 39
- Issue
- 1
- Pages
- 73-84
- ISSN
- 0969-9961 (ISSN-L)
- PMC
- PMC2874108
- OpenAlex
- W2021313742
- Cited by
- 144
- References
- 202
- Citations by year
- 2026: 3 · 2024: 3 · 2023: 6 · 2022: 1 · 2021: 7 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 7 · 2016: 12 · 2015: 14 · 2014: 18 · 2013: 19 · 2012: 16
- FWCI
- 1.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Citizens United for Research in Epilepsy
- National Science Council
- National Institute on Aging (R01AG032383)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- epigenetics, adult hippocampal neurogenesis, neuropsychiatric disorders, neural stem cells, dentate gyrus granule cells, neurogenic niche, DNA methylation, histone modifications, non-coding RNA, depression, neural stem cell differentiation, cell proliferation, epigenetic therapy
- MeSH terms
- Animals, Mental Disorders, Hippocampus, Humans, Genome, Human, Epigenesis, Genetic, Neurogenesis
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