FGF2 is a target and a trigger of epigenetic mechanisms associated with differences in emotionality: Partnership with H3K9me3
Open accessAbstract
Significance: This study investigates the role of epigenetics as a predisposing factor that modifies inborn emotional reactivity and the vulnerability or resilience to affective disorders, such as major depression or substance abuse. It tests the hypothesis that specific modified histones contribute to basal differences in temperament that bias emotional responses to the environment. It further describes the role of a growth factor that can modify these epigenetic patterns as it alters affective behavior.
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H3K9me3 suppresses GR expression in the amygdala and hippocampus in a manner that attenuates HPA axis hyperactivity.
“This increase was concomitant with a decrease in GR expression, suggesting that H3K9me3 suppresses GR expression in these brain regions in a manner that attenuates HPA axis hyperactivity, a factor underscoring the anxiety response (Chaudhury et al., 2014).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Chaudhury et al., 2014
Elevated levels of H3K9me3 associated with the GR promoter were detected in the amygdala and hippocampus of bHR rats (low anxiety) compared with their anxious bLR counterparts.
“Last, elevated levels of H3K9me3 associated with the GR promoter was detected in the amygdala and hippocampus of bHR rats (low anxiety) compared with their anxious bLR counterparts.”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Chaudhury et al., 2014
Cites
Daskalakis, N. P., Bagot, R. C., Parker, K. J., Vinkers, C. H., & de Kloet, E. R. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.06.008 · Cited by 579 · see citing works
The Fibroblast Growth Factor Family: Neuromodulation of Affective Behavior
Turner, C. A., Watson, S. J., & Akil, H. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.037 · Cited by 160 · see citing works
Self-citationSchroeder, F. A., Penta, K. L., Matevossian, A., Jones, S. R., Konradi, C., Tapper, A. R., & Akbarian, S. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.15 · Cited by 139 · see citing works
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Revisiting the Stress Concept: Implications for Affective Disorders
McEwen, B. S., & Akil, H. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.0733-19.2019 · Cited by 686 · see citing works
“…treatment during early life results in epigenetic changes to GR in the hippocampus, increasing its association with a repressive histone, H3K9Me3 (Chaudhury et al., 2014), once again illustrating the role of both glucocorticoids and growth factors as organizing molecules that function during…”
BackgroundSelf-citationBartlett, A. A., Singh, R., & Hunter, R. G. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-53889-1_8 · Cited by 91 · see citing works
Persaud, N. S., & Cates, H. M. (2023) · eneuro · doi:10.1523/eneuro.0109-21.2021 · Cited by 41 · see citing works
Epigenetic mechanisms within the cingulate cortex regulate innate anxiety-like behavior
Sah, A., Sotnikov, S., Kharitonova, M., Schmuckermair, C., Diepold, R. P., Landgraf, R., Whittle, N., & Singewald, N. (2019) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyz004 · Cited by 24 · see citing works
Cognition and mood-related behaviors in L3mbtl1 null mutant mice
Shen, E. Y., Jiang, Y., Mao, W., Futai, K., Hock, H., & Akbarian, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0121252 · Cited by 4 · see citing works
- Authors
- Chaudhury, S., Aurbach, E. L., Sharma, V., Blandino, P., Turner, C. A., Watson, S. J., & Akil, H.
- Affiliations
- Molecular and Behavioral Neuroscience Institute and
- University of Michigan (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-07-28
- Volume
- 111
- Issue
- 32
- Pages
- 11834-11839
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4136576
- OpenAlex
- W2042287782
- Cited by
- 46
- References
- 3
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 1 · 2022: 8 · 2021: 2 · 2020: 3 · 2019: 7 · 2018: 3 · 2017: 6 · 2016: 7 · 2015: 5
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Hope for Depression Research Foundation
- National Institutes of Health
- Office of Naval Research (N00014-09–1-0598 and N00014-12–1-0366, N00014-12-1-0366, N00014‐09‐1‐0598, N00014-12-1, N00014)
- National Institute of Mental Health (R01MH104261)
- National Institute on Drug Abuse (P01DA021633)
- National Institute of Neurological Disorders and Stroke (T32NS076401)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- FGF2, H3K9me3, histone modifications, epigenetic regulation, emotionality, anxiety-like behavior, glucocorticoid receptor, selective breeding, hippocampus, amygdala, nucleus accumbens, early life experience, emotional vulnerability, depression-like behavior, addiction-like behavior
- MeSH terms
- Affect, Animals, Behavior, Animal, Emotions, Hippocampus, Histones, Promoter Regions, Genetic, Receptors, Glucocorticoid, Fibroblast Growth Factor 2, DNA Methylation, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Rats, Gene Knockdown Techniques
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