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Chronic Mild Stressors and Diet Affect Gene Expression Differently in Male and Female Rats

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Abstract

While depression is reportedly more prevalent in women than men, a neurobiological basis for this difference has not been documented. Chronic mild stress (CMS) is a widely recognized animal model, which uses mild and unpredictable environmental stressors to induce depression. Studies of chronic stress, mainly in males, have reported an increase in the relative intake of “comfort food” as a means of counteracting the effects of stress. This study was designed to test the hypothesis that genes for certain neurotrophic factors, stress markers, and appetite regulators would be expressed differentially in male and female rats exposed to chronic, mild stressors with access to a preferred diet. Gene expression for neuropeptide Y was upregulated in females purely in response to stressors, whereas that for the epidermal growth factor receptor (EGFR) and arginine vasopressin (AVP) in males and fatty acid synthase (FASN) in females responded primarily to diet. Genes for brain-derived neurotrophic factor (BDNF), AVP, and the cocaine–amphetamine regulator of transcription (CART) in males, and leptin in females, showed a significant response to the interaction between stressors and diet. Every affected gene showed a different pattern of expression in males and females. This study confirms the intimate relationship between dietary intake and response to stress at the molecular level, and emphasizes the sex- and gene-specific nature of those interactions. Therefore, it supports a neurobiological basis for differences in the affective state response to stress in males and females.

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Acknowledgment

L.I. was supported by grants from NIH-NICDC (#R15-DC005179), and NIH-NCRR-RCMI (#G12-RR08124) to the University of Texas at El Paso. We thank Drs. Kristin Gosselink and Kristine Garza for their helpful advice.

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Correspondence to Shuwen Liang.

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Influence of stages of the female estrus cycle on the expression of growth factor genes in the hypothalamus (Hpy) and amygdala (Amy). Data from individual rats were plotted as scatter diagrams with the medians indicated by horizontal lines. The 1-way ANOVA test of Kruskal-Wallis (GraphPad Prism® 4.0) revealed no correlation between gene expression and different stages of the estrus cycle (GIF 50 KB)

Below is the image is a link to a high resolution version.

Suppl Fig. 2

Influence of stages of the female estrus cycle on the expression of stress marker genes in the hypothalamus (Hpy) and amygdala (Amy). Data from individual rats were plotted as scatter diagrams with the medians indicated by horizontal lines. The 1-way ANOVA test of Kruskal-Wallis (GraphPad Prism® 4.0) revealed no correlation between gene expression and different stages of the estrus cycle (GIF 52 KB)

Below is the image is a link to a high resolution version.

Suppl Fig. 3

Influence of stages of the female estrus cycle on the expression of appetite regulator genes in the hypothalamus (Hpy) and amygdala (Amy). Data from individual rats were plotted as scatter diagrams with the medians indicated by horizontal lines. The 1-way ANOVA test of Kruskal-Wallis (GraphPad Prism® 4.0) revealed no correlation between gene expression and different stages of the estrus cycle (GIF 49 KB)

Below is the image is a link to a high resolution version.

Suppl Fig. 4

Influence of stages in female estrus cycle on the expression of FASN in hypothalamus (Hpy) and amygdala (Amy). Data from individual rats were plotted as scatter diagrams with the medians indicated by horizontal lines. The 1-way ANOVA test of Kruskal-Wallis (GraphPad Prism® 4.0) revealed no correlation between FASN gene expression and different stages of the estrus cycle (GIF 43 KB)

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Liang, S., Byers, D.M. & Irwin, L.N. Chronic Mild Stressors and Diet Affect Gene Expression Differently in Male and Female Rats. J Mol Neurosci 33, 189–200 (2007). https://doi.org/10.1007/s12031-007-0064-x

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  • DOI: https://doi.org/10.1007/s12031-007-0064-x

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