Altered brain morphology and functional connectivity reflect a vulnerable affective state after cumulative multigenerational stress in rats

摘要: Prenatal stress is a risk factor for abnormal neuroanatomical, cognitive, behavioral and mental health outcomes with potentially transgenerational consequences. Females in general seem more resilient to the effects of prenatal than males. Here, we examined if repeated across generations may diminish resiliency cumulatively enhance susceptibility adverse females. Pregnant female rats three successive were exposed from gestational days 12-18 generate multigenerational (MPS) maternal lineage. Stress response was measured by plasma corticosterone levels open-field exploration each generation. Neuromorphological consequences MPS investigated F3 generation using vivo manganese-enhanced magnetic resonance imaging (MEMRI), T2-relaxometry, cytoarchitectonics relation candidate gene expression involved brain plasticity health. Each additional incrementally elevated hypothalamic-pituitary-adrenal axis activation, anxiety-like aversive behaviors adult offspring. Elevated responses accompanied reduced neural density prefrontal cortex, hippocampus whole along altered activation patterns MEMRI. increased ephrin receptor A5 (Epha5), neuronal growth regulator (Negr1) synaptosomal-associated protein 25 (Snap25) fibroblast 12 (Fgf12) cortex. These genes regulate maturation, arborization synaptic explain connectivity. findings emphasize that recurrent increase vulnerability through perinatal programing