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Sex difference in mouse hypothalamic transcriptome profile in stress-induced depression model.
Bhanu Chandra Karisetty1, Nitin Khandelwal2, Arvind Kumar3
1Centre for Chemical Biology, CSIR- Indian Institute of Chemical Technology, Hyderabad, India; Academy of Scientific and Innovative Research, New Delhi, India.
Biochemical and Biophysical Research Communications
|April 8, 2017
Summary
Stress impacts depression differently in males and females, with distinct hypothalamic gene expression patterns observed in mice. Ovarian hormones significantly influence these sex-specific responses to chronic stress.
Area of Science:
- Neuroscience
- Genomics
- Endocrinology
Background:
- Depression prevalence and presentation vary by sex, highlighting the need to study sex influences.
- The hypothalamus, a sexually dimorphic brain region, is implicated in stress responses and depression.
- Chronic stress affects the incidence and progression of depressive phenotypes.
Purpose of the Study:
- To investigate sex-specific transcriptional changes in the hypothalamus induced by chronic stress.
- To determine the role of ovarian hormones in stress-regulated hypothalamic gene expression.
- To identify key pathways and genes involved in sex-specific depression phenotypes.
Main Methods:
- Utilized a chronic variable mild stress model in male, intact female, and ovariectomized female mice.
- Performed gene-array analysis to identify stress-regulated genes in the hypothalamus (fold change >1.2, p < 0.05).
- Assessed depression-like behavior using the forced swim test and conducted pathway analysis on altered genes.
Main Results:
- Identified unique sets of stress-regulated genes in males (90), intact females (205), and ovariectomized females (106).
- 'Posttranslational processing of neuroendocrine peptides' was the most significantly enriched and differentially regulated pathway.
- Observed differential regulation of arginine vasopressin, cholecystokinin, and oxytocin, with sex- and hormone-dependent patterns.
Conclusions:
- Stress-regulated hypothalamic transcriptional changes are sex-specific and ovarian hormone-dependent.
- Intact females exhibit a more intricate molecular response to chronic stress.
- Findings underscore the necessity for sex-based medical attention in depressive disorder treatment.