Cited by 240Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorStress Responses and Cortisol

Cellular and molecular basis for stress-induced depression

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Seo, J-S, Wei, J, Qin, L, Kim, Y, Yan, Z, Greengard, P·2017·Molecular Psychiatry

Abstract

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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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
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
Open access
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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