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

产前应激影响哺乳动物新皮质发育和对应激的长期神经行为反应

• 批准号: 436204-2013
• 负责人: Weaver, Ian
• 金额: $ 2.33万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630105
• 关键词: Prenatal; stress; affects; mammalian; neocortex

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.

该研究项目旨在研究早期环境经验如何影响哺乳动物的大脑发育和成年行为。糖皮质激素（GC）-一种在胎儿发育过程中起重要作用的类固醇激素-作为产科和围产期医学中许多疾病的标准治疗方法，但GC暴露增加对大脑早期发育的影响仍然未知。研究表明，GC对后代有深远的影响，影响社会，情感和认知发展，这是终身忍受。与环境引起的影响的持久性有关的机制仍然是一个问题：什么生物和行为途径可以导致GC影响的持续性？当然，产前环境起着重要的发育作用，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改变是一个候选机制。Weaver博士的研究计划旨在研究GC暴露对大脑一部分（皮层）神经元发育的影响。更具体地说，他将研究胚胎发育过程中暴露于GC后有限的皮质神经干细胞库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，并一直持续到成年。Weaver博士的研究项目将采用综合、比较和多学科的方法，在神经和行为层面上深入了解对早期环境压力源的适应性反应。从生物学的角度来看，解开产前GC暴露对后代特定内分泌和行为结果的长期影响，可能会提供新的洞察力的弹性和脆弱性的压力机制。这项工作的结果也可能有重要的影响，为未来的研究检查产前和围产期的经验对适应性脑功能的影响。