Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zürich, Schwerzenbach, Switzerland.
Psychopharmacology (Berl). 2011 Mar;214(1):33-53. doi: 10.1007/s00213-010-1989-2. Epub 2010 Sep 1.
Exposure of the immature mammalian brain to stress factors, including stress levels of glucocorticoids, either prenatally or postnatally, is regarded as a major regulatory factor in short- and long-term brain function and, in human, as a major aetiological factor in neuropsychiatric disorders. Experimental human studies are not feasible and animal studies are required to demonstrate causality and elucidate mechanisms. A number of studies have been conducted and reviewed in rodents but there are relatively few studies in primates.
Here we present an overview of our published studies and some original data on the effects of: (1) prenatal stress on hypothalamic-pituitary-adrenal (HPA) re/activity and hippocampus neuroanatomy in juvenile-adolescent rhesus macaques; (2) prenatal dexamethasone (DEX) on HPA activity, behaviour and prefrontal cortex neuroanatomy in infant-adolescent common marmosets; (3) postnatal daily parental separation stress on HPA re/activity, behaviour, sleep and hippocampus and prefrontal cortex neuroanatomy in infant-adolescent common marmoset.
Prenatal stress increased basal cortisol levels and reduced neurogenesis in macaque. Prenatal DEX was without effect on HPA activity and reduced social play and skilled motor behaviour in marmoset. Postnatal social stress increased basal cortisol levels, reduced social play, increased awakening and reduced hippocampal glucocorticoid and mineralocorticoid receptor expression in marmoset.
Perinatal stress-related environmental events exert short- and long-term effects on HPA function, behaviour and brain status in rhesus macaque and common marmoset. The mechanisms mediating the enduring effects remain to be elucidated, with candidates including increased basal HPA function and epigenetic programming.
在哺乳动物大脑发育过程中,无论是产前还是产后,暴露于应激因素(包括糖皮质激素水平)被认为是短期和长期大脑功能的主要调节因素,而在人类中,则是神经精神疾病的主要病因因素。由于无法进行人体实验,因此需要动物实验来证明因果关系并阐明相关机制。虽然已经在啮齿动物中进行了许多研究并进行了综述,但在灵长类动物中相对较少。
在这里,我们概述了我们已发表的研究以及一些关于以下方面的原始数据:(1)产前应激对幼年恒河猴下丘脑-垂体-肾上腺(HPA)反应性和海马神经解剖结构的影响;(2)产前地塞米松(DEX)对婴儿期-青少年普通狨猴 HPA 活性、行为和前额叶皮质神经解剖结构的影响;(3)婴儿期-青少年普通狨猴产后每天父母分离应激对 HPA 反应性、行为、睡眠以及海马和前额叶皮质神经解剖结构的影响。
产前应激增加了猕猴的基础皮质醇水平并减少了神经发生。产前 DEX 对 HPA 活性没有影响,但减少了狨猴的社会玩耍和熟练运动行为。产后社会压力增加了基础皮质醇水平,减少了社会玩耍,增加了觉醒,并减少了狨猴海马中的糖皮质激素和盐皮质激素受体表达。
围产期应激相关的环境事件对恒河猴和普通狨猴的 HPA 功能、行为和大脑状态产生短期和长期影响。介导持久效应的机制仍有待阐明,候选机制包括基础 HPA 功能增加和表观遗传编程。