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Repeated swim-stress reduces GABAA receptor alpha subunit mRNAs in the mouse hippocampus
P Montpied1, A Weizman, R Weizman
1Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Abstract:
The effects of brief repeated swim stress on the expression of GABAA receptor alpha 1 subunit mRNAs was investigated in the mouse. Adult male mice were exposed to repeated brief (10 min) swim-stress once daily for 7 or 14 days and the levels of GABAA receptor alpha subunit mRNAs were quantified in the hippocampus 24 h after the last session by Northern analysis. Repeated swim stress for 14 days resulted in a 47.3% +/- 6.5 and 39.8% +/- 7.6 decrease in the levels of the 4.8 kb and 4.4 kb GABAA receptor alpha 1 subunit mRNAs, respectively. While there was a trend toward a reduction in the level of GABAA receptor alpha 1 subunit mRNAs following 7 days of repeated swim stress, the latter did not reach statistical significance. In contrast, no significant alterations in the levels of glutamic acid decarboxylase or beta-actin mRNAs were observed at either time point. The reduction in GABAA receptor alpha 1 subunit mRNAs following repeated swim stress may underlie similar alteration(s) in hippocampal GABAA receptor density previously observed following repeated swim stress.
Insights
Repeated swim stress in mice significantly reduced GABA-A receptor alpha 1 subunit messenger RNAs (mRNAs) in the hippocampus after 14 days. This stress-induced change in mRNA levels may explain alterations in hippocampal GABA-A receptor density.
Area of Science:
- Neuroscience
- Molecular Biology
- Stress Research
Background:
- The GABA-A receptor is a key inhibitory neurotransmitter receptor in the brain.
- Stress can significantly impact neuronal function and gene expression.
- Previous studies suggest alterations in hippocampal GABA-A receptor density following chronic stress.
Purpose of the Study:
- To investigate the effects of repeated brief swim stress on GABA-A receptor alpha 1 subunit mRNA expression in the mouse hippocampus.
- To determine the time course of these changes, examining stress durations of 7 and 14 days.
Main Methods:
- Adult male mice were subjected to daily 10-minute swim stress sessions.
- mRNA levels of the GABA-A receptor alpha 1 subunit were quantified using Northern analysis.
- Levels were measured 24 hours after the final stress session.
- Expression of glutamic acid decarboxylase and beta-actin mRNAs were also assessed as controls.
Main Results:
- Fourteen days of repeated swim stress led to a significant decrease in both 4.8 kb (47.3%) and 4.4 kb (39.8%) GABAA receptor alpha 1 subunit mRNA levels.
- Seven days of stress showed a trend towards reduced mRNA levels, but this did not reach statistical significance.
- No significant changes were observed in glutamic acid decarboxylase or beta-actin mRNA levels at either time point.
Conclusions:
- Repeated brief swim stress, particularly over 14 days, downregulates the expression of GABAA receptor alpha 1 subunit mRNAs in the mouse hippocampus.
- These molecular changes in mRNA levels provide a potential mechanism for previously observed alterations in hippocampal GABAA receptor density due to chronic stress.