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Extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone.

Title: Extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone.
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Name(s): Carrier, Nicole, author
Kabbaj, Mohamed, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2012-04-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Human and animal studies suggest that testosterone may have antidepressant effects. In this study, we sought to investigate the molecular mechanisms underlying the antidepressant effects of testosterone within the hippocampus, an area that is fundamental in the etiology of depression. The effects of testosterone replacements in gonadectomized adult male rats were investigated using the sucrose preference and forced swim tests. We explored possible effects of testosterone on hippocampal neurogenesis and gene expression of stress-related molecules. Through the use of viral vectors, we pursued the antidepressant molecular mechanism(s) of testosterone in mediating anhedonia and manipulated extracellular signal-regulated kinase 2 (ERK2) expression in the dentate gyrus in gonadectomized rats with testosterone replacements. Testosterone had antidepressant effects, likely mediated by aromatization to estrogen metabolites, in the sucrose preference and forced swim tests despite having no effects on hippocampal cell proliferation or survival. We found a testosterone-dependent regulation of hippocampal ERK2 expression. Functionally, reducing ERK2 activity within the dentate gyrus induced anhedonia in gonadectomized rats receiving testosterone supplementation, whereas the overexpression of ERK2 rescued this behavior in gonadectomized rats. These results implicate a role for ERK2 signaling within the dentate gyrus area of the hippocampus as a key mediator of the antidepressant effects of testosterone.
Identifier: FSU_pmch_22265242 (IID), 10.1016/j.biopsych.2011.11.028 (DOI), PMC3307821 (PMCID), 22265242 (RID), 22265242 (EID), S0006-3223(11)01201-7 (PII)
Grant Number: R01 MH087583-02, R01MH087583, R01 MH087583-01A1, R01 MH087583, R01 MH087583-03
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307821.
Subject(s): Anhedonia/drug effects
Animals
Antidepressive Agents/metabolism
Antidepressive Agents/pharmacology
Brain-Derived Neurotrophic Factor/biosynthesis
Cell Proliferation/drug effects
Cell Survival/drug effects
Choice Behavior/drug effects
Dentate Gyrus/drug effects
Dentate Gyrus/metabolism
Disease Models, Animal
Gene Expression/drug effects
Immobility Response, Tonic/drug effects
Male
Mitogen-Activated Protein Kinase 1/genetics
Mitogen-Activated Protein Kinase 1/metabolism
Motor Activity/drug effects
Neurogenesis/drug effects
Rats
Rats, Sprague-Dawley
Rats, Transgenic
Receptors, Glucocorticoid/biosynthesis
Testosterone/analogs & derivatives
Testosterone/blood
Testosterone/pharmacology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_22265242
Owner Institution: FSU
Is Part Of: Biological psychiatry.
1873-2402
Issue: iss. 7, vol. 71

Choose the citation style.
Carrier, N., & Kabbaj, M. (2012). Extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone. Biological Psychiatry. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_22265242