Abstract
BackgroundStress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults.MethodsDorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys.ResultsExtensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex.ConclusionsStress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.
Highlights
Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men
We examined gene expression profiles for dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from female and male squirrel monkey adults randomly selected from a larger sample randomized to stress or no-stress conditions
Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex
Summary
Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. We investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults. Mood and anxiety disorders occur more often in women than men [1,2,3,4] These mental health disorders are associated with stress-induced modifications in prefrontal cortex [5,6,7]. Neuroscience research has until recently focused on males [8], and sex differences in stress effects on primate prefrontal profiles of gene expression are not known. Sex differences and stress effects in squirrel monkey prefrontal cortical profiles of gene expression may provide insights on the biology of sex differences in human mental health
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