Social Defeat during Adolescence and Adulthood Differentially Induce BDNF-Regulated Immediate Early Genes
Open accessAbstract
Stressful life events generally enhance the vulnerability for the development of human psychopathologies such as anxiety disorders and depression. The incidence rates of adult mental disorders steeply rises during adolescence in parallel with a structural and functional reorganization of the neural circuitry underlying stress reactivity. However, the mechanisms underlying susceptibility to stress and manifestation of mental disorders during adolescence are little understood. We hypothesized that heightened sensitivity to stress during adolescence reflects age-dependent differences in the expression of activity-dependent genes involved in synaptic plasticity. Therefore, we compared the effect of social stress during adolescence with social stress in adulthood on the expression of a panel of genes linked to induction of long-term potentiation (LTP) and brain-derived neurotrophic factor (BDNF) signaling. We show that social defeat during adolescence and adulthood differentially regulates expression of the immediate early genes BDNF, Arc, Carp, and Tieg1, as measured by qPCR in tissue lysates from prefrontal cortex, nucleus accumbens, and hippocampus. In the hippocampus, mRNA levels for all four genes were robustly elevated following social defeat in adolescence, whereas none were induced by defeat in adulthood. The relationship to coping style was also examined using adult reactive and proactive coping rats. Gene expression levels of reactive and proactive animals were similar in the prefrontal cortex and hippocampus. However, a trend toward a differential expression of BDNF and Arc mRNA in the nucleus accumbens was detected. BDNF mRNA was increased in the nucleus accumbens of proactive defeated animals, whereas the expression level in reactive defeated animals was comparable to control animals. The results demonstrate striking differences in immediate early gene expression in response to social defeat in adolescent and adult rats.
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Transcription factors downstream of BDNF, including transforming growth factor β-inducible early gene-1 and Egr3, are upregulated after social defeat.
“Transcription factors downstream of BDNF, such as transforming growth factor β-inducible early gene-1 [102], and Early Growth Response 3 (Egr3) [88] are also upregulated after social defeat (Fig. 2, middle).”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [102]
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References 73 · Cited by 61
- Authors
- Coppens, C. M., Siripornmongcolchai, T., Wibrand, K., Alme, M. N., Buwalda, B., de Boer, S. F., Koolhaas, J. M., & Bramham, C. R.
- Affiliations
- University of Groningen (NL)
- University of Bergen (NO)
- Corresponding author
- Coppens, Caroline M.
- Venue
- Frontiers in Behavioral Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2011
- Volume
- 5
- Pages
- 72-72
- ISSN
- 1662-5153 (ISSN-L)
- PMC
- PMC3206404
- OpenAlex
- W2063973705
- Cited by
- 61
- References
- 73
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 9 · 2015: 2 · 2014: 4 · 2013: 10 · 2012: 3
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- European Science Foundation
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- European Social Fund
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- social defeat, adolescence, adulthood, brain-derived neurotrophic factor, immediate early genes, Arc, carp, TIEG1, stress reactivity, coping styles, proactive coping, reactive coping, hippocampus, nucleus accumbens, prefrontal cortex, synaptic plasticity, long-term potentiation, anxiety, depression
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