Cellular and molecular basis for stress-induced depression
Open accessAbstract
Chronic stress has a crucial role in the development of psychiatric diseases, such as anxiety and depression. Dysfunction of the medial prefrontal cortex (mPFC) has been linked to the cognitive and emotional deficits induced by stress. However, little is known about the molecular and cellular determinants in mPFC for stress-associated mental disorders. Here we show that chronic restraint stress induces the selective loss of p11 (also known as annexin II light chain, S100A10), a multifunctional protein binding to 5-HT receptors, in layer II/III neurons of the prelimbic cortex (PrL), as well as depression-like behaviors, both of which are reversed by selective serotonin reuptake inhibitors (SSRIs) and the tricyclic class of antidepressant (TCA) agents. In layer II/III of the PrL, p11 is highly concentrated in dopamine D2 receptor-expressing (D2 + ) glutamatergic neurons. Viral expression of p11 in D2 + PrL neurons alleviates the depression-like behaviors exhibited by genetically manipulated mice with D2 + neuron-specific or global deletion of p11. In stressed animals, overexpression of p11 in D2 + PrL neurons rescues depression-like behaviors by restoring glutamatergic transmission. Our results have identified p11 as a key molecule in a specific cell type that regulates stress-induced depression, which provides a framework for the development of new strategies to treat stress-associated mental illnesses.
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Prolonged exposure to stress increases vulnerability to mood disorders, including depression.
“Prolonged exposure to stress increases vulnerability to mood disorders, including depression [2, 3].”
From Chronic stress-induced depression requires the recruitment of peripheral Th17 cells into the brain (2022) · cites this paper as [2]
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- Authors
- Seo, J.-S., Wei, J., Qin, L., Kim, Y., Yan, Z., & Greengard, P.
- Affiliations
- Rockefeller University (US)
- University at Buffalo, State University of New York (US)
- Corresponding author
- Greengard, P
- Venue
- Molecular Psychiatry
- Published
- 2016-07-26
- Volume
- 22
- Issue
- 10
- Pages
- 1440-1447
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5269558
- OpenAlex
- W2495465436
- Cited by
- 235
- References
- 44
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 33 · 2023: 33 · 2022: 33 · 2021: 29 · 2020: 13 · 2019: 19 · 2018: 18 · 2017: 5
- FWCI
- 11.33
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-10-22)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W81XWH0910402, W81XWH)
- Fisher Center for Alzheimer's Research Foundation
- JPB Foundation
- Debra and Leon Black Family Foundation
- National Institutes of Health (W81XWH, UL1TR001412, MH108842)
- National Institute of Mental Health (P50MH090963, MH108842, R01MH108842)
- National Institute on Drug Abuse (R01DA037618, P01DA010044)
- National Center for Advancing Translational Sciences
- U.S. Army Medical Research Acquisition Activity
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- chronic restraint stress, stress-induced depression, p11, S100A10, medial prefrontal cortex, prelimbic cortex, dopamine D2 receptor, glutamatergic neurons, selective serotonin reuptake inhibitors, tricyclic antidepressants, depression-like behavior, serotonin receptors, glutamatergic neurotransmission
- MeSH terms
- S100 Calcium Binding Protein A10, Animals, Anxiety Disorders, Chronic Disease, Depression, Depressive Disorder, Emotions, Humans, Mice, Transgenic, S100 Proteins, Neurons, Receptors, Serotonin, Stress, Psychological, Annexin A2, Selective Serotonin Reuptake Inhibitors, Prefrontal Cortex, Receptors, Dopamine D2, Mice
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