Abstract
Serotonin (5-HT) is implicated in the development of stress-related mood disorders in humans. Physical activity reduces the risk of developing stress-related mood disorders, such as depression and anxiety. In rats, 6 weeks of wheel running protects against stress-induced behaviors thought to resemble symptoms of human anxiety and depression. The mechanisms by which exercise confers protection against stress-induced behaviors, however, remain unknown. One way by which exercise could generate stress resistance is by producing plastic changes in gene expression in the dorsal raphe nucleus (DRN). The DRN has a high concentration of 5-HT neurons and is implicated in stress-related mood disorders. The goal of the current experiment was to identify changes in the expression of genes that could be novel targets of exercise-induced stress resistance in the DRN. Adult, male F344 rats were allowed voluntary access to running wheels for 6 weeks; exposed to inescapable stress or no stress; and sacrificed immediately and 2 h after stressor termination. Laser capture micro dissection selectively sampled the DRN. mRNA expression was measured using the whole genome Affymetrix microarray. Comprehensive data analyses of gene expression included differential gene expression, log fold change (LFC) contrast analyses with False Discovery Rate correction, KEGG and Wiki Web Gestalt pathway enrichment analyses, and Weighted Gene Correlational Network Analysis (WGCNA). Our results suggest that physically active rats exposed to stress modulate expression of twice the number of genes, and display a more rapid and strongly coordinated response, than sedentary rats. Bioinformatics analyses revealed several potential targets of stress resistance including genes that are related to immune processes, tryptophan metabolism, and circadian/diurnal rhythms.
Highlights
Depression and anxiety frequently coexist and are the most common mood disorders affecting society
The effect of stress on differential gene expression is different depending on physical activity status
The effect of stress on differential expression of genes in the dorsal raphe nucleus (DRN) is different depending on physical activity status
Summary
Depression and anxiety frequently coexist and are the most common mood disorders affecting society. The World Health Organization estimates that 121 million people currently suffer from depression. Individuals suffering from depression have significant impairment in quality of life (Rapaport et al, 2005), are at increased risk for developing coronary heart disease (Wulsin and Singal, 2003) and type 2 diabetes (Knol et al, 2006), and have higher mortality due to suicide. Stressful life events often precede the onset of depression (Kendler et al, 1999; van Praag, 2005) and anxiety. Important to note is that not every individual who experiences a stressful life event develops a serious mood disorder, and these individuals may possess resistance to the negative affective consequences of stress. Pinpointing the factors by which stress resistance occurs could provide a better understanding of the neurobiological mechanisms underlying stress-related mood disruptions
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