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Hippocampal gene expression changes underlying stress sensitization and recovery
J D Gray1, T G Rubin1, R G Hunter2
1Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, USA.
Molecular Psychiatry
|December 18, 2013
Summary
Chronic stress alters hippocampal gene expression and anxiety behaviors, with some changes persisting long-term. This study reveals lasting gene expression changes in the hippocampus after chronic stress, impacting stress response.
Area of Science:
- Neuroscience
- Molecular Biology
- Behavioral Science
Background:
- Chronic and acute stressors impact hippocampal function and anxiety-like behaviors.
- Stress-induced gene expression changes are not fully understood, especially their persistence post-stress.
Purpose of the Study:
- To characterize enduring gene expression patterns in the hippocampus following chronic restraint stress (CRS).
- To investigate how prior CRS influences the response to a novel stressor.
- To examine the lasting effects of CRS on hippocampal gene expression and anxiety-like behaviors.
Main Methods:
- Male C57/bl6 mice were exposed to forced swim test (FST), corticosterone (Cort) injections, CRS, or recovery post-CRS.
- Hippocampal mRNA was analyzed using microarray hybridization.
- Quantitative reverse transcription-PCR (qRT-PCR) validated key gene expression changes, including the NF-κB pathway.
Main Results:
- Novel stress exposure after CRS activated more genes than naive stressors.
- Many stress-induced gene expression changes persisted after recovery, indicating permanent alterations.
- The nuclear factor kappa-light-chain-enhancer of B cells (NF-κB) pathway was significantly affected.
- Anxiety-like behaviors were altered by FST, with responses differing based on prior stress exposure.
Conclusions:
- Prior stress exposure permanently alters hippocampal gene expression and behavioral responses to novel stressors.
- Naive stress effects differ from corticosterone elevation.
- Findings provide a baseline for studying stress recovery and impaired adaptation in mood and anxiety disorders.
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