Early life stress confers lifelong stress susceptibility in mice via ventral tegmental area OTX2
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An early window of stress susceptibility defines a mouse’s response to stress in adulthood.
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Early life stress may not cause immediate behavioral abnormalities but instead causes long-lasting transcriptional alterations that prime critical brain regions to be hyper-responsive to later stress and prone to develop a depression-like state.
“ELS may not cause immediate behavioral abnormalities but instead causes long-lasting transcriptional alterations that prime critical brain regions to be hyper-responsive to later stress and prone to develop a depression-like state.209,210”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [209]
In a two-hit stress model in mice, early life stress increased susceptibility to depression-like behavior in response to social defeat stress during adulthood.
“This was illustrated by a “two-hit” stress model in mice wherein ELS (stress hit number 1) increased susceptibility to depression-like behavior in response to social defeat stress (stress hit number 2) during adulthood.209”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [209]
Social behavior impairments as a consequence of early life stress seem to stem from aberrations of the DA system, including long-lasting transcriptional changes in VTA DA neurons and impaired DA signaling in the lateral septum.
“Social behavior impairments as a consequence of early life stress also seem to stem from aberrations of the DA system, including long-lasting transcriptional changes in VTA DA neurons [151] and impaired DA signaling in the lateral septum [152].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [151]
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“209 Enduring transcriptional alterations were observed in the ventral tegmental area (VTA) in ELS, mediated by the developmental transcription factor orthodenticle homeobox 2 (OTX2).”
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- Authors
- Peña, C. J., Kronman, H. G., Walker, D. M., Cates, H. M., Bagot, R. C., Purushothaman, I., Issler, O., Loh, Y.-H. E., Leong, T., Kiraly, D. D., Goodman, E., Neve, R. L., Shen, L., & Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Nestler, Eric J.
- ORCID
- Venue
- Science
- Published
- 2017-06-16
- Volume
- 356
- Issue
- 6343
- Pages
- 1185-1188
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5539403
- OpenAlex
- W2626018769
- Cited by
- 394
- References
- 41
- Citations by year
- 2026: 31 · 2025: 44 · 2024: 51 · 2023: 41 · 2022: 35 · 2021: 50 · 2020: 34 · 2019: 47 · 2018: 46 · 2017: 13
- FWCI
- 20.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (award310877, P50MH096890)
- Hope for Depression Research Foundation (award310878, EJN)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- early life stress, stress vulnerability, ventral tegmental area, Otx2, brain development, stress response, mice
- MeSH terms
- Age Factors, Animals, Depression, Female, Gene Expression Regulation, Male, Mice, Inbred C57BL, Protein Binding, Stress, Physiological, Ventral Tegmental Area, Mice, Otx Transcription Factors, Gene Knockdown Techniques
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