Prenatal stress affects on mammalian neocortex development and long-term neurobehavioural responses to stress

这项研究项目考察了早期环境体验如何影响哺乳动物的大脑发育和成年行为。糖皮质激素(GCs)是一种在胎儿发育过程中发挥重要作用的类固醇激素，在产科和围产期医学中被用作许多疾病的标准治疗方法，但GC暴露增加对大脑早期生命发育的影响尚不清楚。研究表明，GC对后代有深远的影响，影响社会、情感和认知的发展，这种影响贯穿一生。与环境诱导影响的持续性有关的机制仍然存在疑问：哪些生物和行为途径可以导致GCs影响的连续性？当然，产前环境对发育起着重要的作用，在母体传递压力效应的情况下，与胎儿发育相关的激素水平的变化是一个候选机制。韦弗博士的研究建议旨在研究GC暴露对大脑某一部分(大脑皮层)神经元发育的影响。更具体地说，他将研究胚胎发育期间GC暴露后有限的皮质神经干细胞池的命运，以及这种暴露对大脑结构的影响。此外，他还将探索潜在的遗传和表观遗传机制，这些机制支持对压力的生理和行为反应的发展，并保持到成年。韦弗的研究计划将采用综合、比较和多学科的方法，在神经和行为层面上提供对早期环境应激源的适应性反应。从生物学的角度来看，揭示产前GC暴露对后代特定内分泌和行为结果的长期影响，可能为了解应激的弹性和脆弱性机制提供新的见解。这项工作的结果也可能对未来检验产前和围产期经历对适应性大脑功能的影响的研究具有重要意义。

This research program examines how early environmental experience affects mammalian brain development and adult behaviour. Glucocorticoids (GCs)-a type of steroid hormone that plays an important role during fetal development-are administered as standard treatment for a number of conditions in obstetrics and perinatal medicine, however the effects of increased GC exposure on early life development of the brain remain unknown. Studies have demonstrated that GCs have a profound influence on offspring, affecting social, emotional and cognitive development, which is endured through life. The mechanism associated with the persistence of environmentally-induced effects remains in question: What biological and behavioural pathways can lead to the continuity of the effects of GCs? Certainly, the prenatal environment plays a significant developmental role and, in the case of the maternal transmission of stress effects, alterations in the levels of hormones associated with fetal development is a candidate mechanism. Dr. Weaver's research proposal aims to examine the effects of GC exposure on the development of neurons in a part of the brain (the cortex). More specifically, he will study the fate of the limited pool of cortical neural stem cells after GC exposure during embryonic development and the impact of this exposure on brain structure. Additionally, he will explore the underlying genetic and epigenetic mechanisms that support the development of physiological and behavioural responses to stress that are maintained into adulthood.Dr. Weaver's research program will provide insight into adaptive responses to early environmental stressors at neural and behavioural levels, using an integrative, comparative and multidisciplinary approach. From a biology perspective, unraveling the long-term effects of prenatal GC exposure on specific endocrine and behavioural outcomes in the offspring may provide new insight into mechanisms of resilience and vulnerability to stress. The results of this work may also have important implications for future studies examining the effects of prenatal and perinatal experiences on adaptive brain function.