Serum Response Factor Promotes Resilience to Chronic Social Stress through the Induction of ΔFosB
Open accessAbstract
The molecular mechanisms underlying stress- and drug-induced neuronal adaptations are incompletely understood. One molecule implicated in such adaptations is ΔFosB, a transcription factor that accumulates in the rodent nucleus accumbens (NAc), a key brain reward region, in response to either chronic stress or repeated exposure to drugs of abuse. The upstream transcriptional mechanisms controlling ΔFosB induction by these environmental stimuli remain elusive. Here, we identify the activity-dependent transcription factor, serum response factor (SRF), as a novel upstream mediator of stress-, but not cocaine-, induced ΔFosB. SRF is downregulated in NAc of both depressed human patients and in mice chronically exposed to social defeat stress. This downregulation of SRF is absent in resilient animals. Through the use of inducible mutagenesis, we show that stress-mediated induction of ΔFosB, which occurs predominantly in resilient mice, is dependent on SRF expression in this brain region. Furthermore, NAc-specific genetic deletion of SRF promotes a variety of prodepressant- and proanxiety-like phenotypes and renders animals more sensitive to the deleterious effects of chronic stress. In contrast, we demonstrate that SRF does not play a role in ΔFosB accumulation in NAc in response to chronic cocaine exposure. Furthermore, NAc-specific knock-out of SRF has no effect on cocaine-induced behaviors, indicating that chronic social defeat stress and repeated cocaine exposure regulate ΔFosB accumulation and behavioral sensitivity through independent mechanisms.
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Selective induction of ΔFosB in the nucleus accumbens of resilient animals is mediated via activation of serum response factor.
“The selective induction of ΔFosB in NAc of resilient animals is mediated via the activation of serum response factor (SRF) under these conditions72”
From Neurobiology of resilience (2012) · cites this paper as [72]
Examples of resilience-associated molecular changes include ΔFosB, SRF, HDAC2, and the WNT-DVL-GSK3β signaling cascade.
“Examples include ΔFosB and SRF, discussed above, as well as HDAC2 (histone deacetylase–2) and the WNT (wingless)–DVL (disheveled)–GSK3β (glycogen synthase kinase–3β) signaling cascade71, 72, 94”
From Neurobiology of resilience (2012) · cites this paper as [72]
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- Authors
- Vialou, V., Maze, I., Renthal, W., LaPlant, Q. C., Watts, E. L., Mouzon, E., Ghose, S., Tamminga, C. A., & Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- The University of Texas Southwestern Medical Center (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2010-10-27
- Volume
- 30
- Issue
- 43
- Pages
- 14585-14592
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2977979
- OpenAlex
- W2002691488
- Cited by
- 91
- References
- 36
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 10 · 2016: 5 · 2015: 9 · 2014: 12 · 2013: 6 · 2012: 11
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- National Institute of Mental Health (R01MH051399)
- National Institute on Drug Abuse (R01DA007359)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- serum response factor, ΔFosB, chronic social stress, social defeat stress, stress resilience, nucleus accumbens, transcriptional regulation, depression, anxiety, cocaine
- MeSH terms
- Adult, Aged, Animals, Antidepressive Agents, Anxiety, Cocaine, Depression, Female, Helplessness, Learned, Humans, Male, Mice, Inbred C57BL, Middle Aged, Motor Activity, Nucleus Accumbens, Social Behavior, Social Environment, Stress, Psychological, Blotting, Western, Proto-Oncogene Proteins c-fos, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Serum Response Factor, Immunoprecipitation, Mice, Resilience, Psychological
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