Cited by 76Treatment of Major DepressionNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Ribosomal protein S6 kinase 1 signaling in prefrontal cortex controls depressive behavior

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Dwyer, Jason M., Maldonado-Avilés, Jaime G., Lepack, Ashley E., DiLeone, Ralph J., Duman, Ronald S.·2015·Proceedings of the National Academy of Sciences

Abstract

Significance: The molecular pathophysiology associated with depression remains largely unknown. Recent evidence suggests that signaling pathways downstream of mechanistic target of rapamycin complex 1, such as p70 S6 kinase 1 (S6K1), can lead to structural changes in the medial prefrontal cortex (mPFC) of rats, which are associated with antidepressant responses. We used a viral-mediated approach to control S6K1 activity in the mPFC. Enhanced S6K1 activity produced antidepressant-like effects and resilience to chronic stress, whereas decreased S6K1 activity produced prodepressive behavior. Together, these studies demonstrate that aberrant activity of protein synthesis pathways may underlie the pathology of depression, and demonstrate that direct modulation of this pathway can control depressive behavior in a bidirectional manner. Further understanding of these signaling pathways may contribute to improved treatments for major depressive disorder.

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Authors
Dwyer, J. M., Maldonado-Avilés, J. G., Lepack, A. E., DiLeone, R. J., & Duman, R. S.
Affiliations
  • Yale University (US)
  • Laboratory of Molecular Psychiatry, Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, CT 06508
Venue
Proceedings of the National Academy of Sciences
Published
2015-04-27
Volume
112
Issue
19
Pages
6188-6193
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W1965008000
Cited by
76
References
24
Citations by year
2026: 4 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 6 · 2019: 12 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 5
FWCI
6.96
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
HHS | National Institutes of Health (MH093897, MH102004)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
mTORC1, major depressive disorder, medial prefrontal cortex, antidepressant effects, anhedonia, chronic stress, stress resilience, forced swim test, synaptic protein synthesis, translational regulation, neuronal complexity
MeSH terms
Animals, Antidepressive Agents, Behavior, Animal, Major Depressive Disorder, Disease Models, Animal, Ketamine, Male, Neurons, Phenotype, Phosphorylation, Swimming, Signal Transduction, Gene Expression Regulation, Enzymologic, Rats, Sprague-Dawley, Prefrontal Cortex, Maze Learning, Ribosomal Protein S6 Kinases, Sirolimus, Rats

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