Overexpression of Forebrain @entity8740 During Early Life Increases XXXX Susceptibility in Adulthood.

@entity20710 @entity19 @entity19484 @entity8740 @entity1005 @entity148 @entity427 @entity22830 @entity130
Although early-life stress is a significant risk factor for developing @entity148 , including @entity1005 ( @entity1005 ), the underlying mechanisms are unclear. @entity8740 ( @entity8740 ) is disrupted in individuals with @entity1005 and early-life stress and hence may mediate the effects of early-life stress on @entity1005 risk. We hypothesized that @entity8740 hyper-signaling in the forebrain during early development is sufficient to increase response to @entity130 in adulthood. To test this hypothesis, we induced transient, forebrain-specific, @entity8740 overexpression during early-life (pre-puberty, CRHOEdev) in double-mutant @entity19 (Camk2a-rtta2 * tetO- @entity8740 ) and tested their behavioral and gene expression responses to the predator stress model of @entity1005 in adulthood. In one cohort of CRHOEdev exposed and unexposed @entity19 , avoidance and arousal behaviors were examined 7-15 days after exposure to predator stress. In another cohort, gene expression changes in @entity22830 , @entity19484 , and @entity20710 in forebrain of CRHOEdev exposed and unexposed @entity19 were examined 7 days after predator stress. CRHOEdev induced robust increases in @entity427 reactivity and reductions in @entity427 inhibition independently of predator stress in both male and female @entity19 . Avoidance behaviors after predator stress were highly dependent on sex and CRHOEdev exposure. Whereas stressed females exhibited robust avoidance responses that were not altered by CRHOEdev, males developed significant avoidance only when exposed to both CRHOEdev and stress. Quantitative real-time-PCR analysis indicated that CRHOEdev unexposed males exhibit significant changes in @entity19484 expression in the amygdala and bed nucleus stria terminalis in response to stress, whereas males exposed to CRHOEdev did not. Similar to CRHOEdev males, females exhibited no significant @entity19484 gene expression changes in response to stress. Cortical @entity20710 expression was also significantly reduced by stress and CRHOEdev exposure in males, but not in females. These findings indicate that forebrain @entity8740 hyper-signaling in early-life is sufficient to increase enduring effects of adult @entity130 and attenuate @entity19484 expression changes in response to stress in males. These data support growing evidence for significant sex differences in response to @entity130 , and support further study of @entity19484 as a candidate mechanism for @entity1005 risk.
