Luoni Alessia, Richetto Juliet, Racagni Giorgio, Molteni Raffaella
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milan, Italy.
Curr Pharm Des. 2015;21(11):1388-95. doi: 10.2174/1381612821666150105142824.
The impact of early physical and social environments on life-long pathological phenotypes is well known and there is now compelling evidence that stressful experiences during gestation or early in life can lead to enhanced susceptibility to mental illness. Here, we discuss the data from preclinical studies aimed at investigating the molecular consequences of the exposure to stressful events during prenatal or early postnatal life that might contribute to later psychopathology. Particularly, we will discuss the existence of age windows of vulnerability to environmental conditions during brain maturation using as examples several studies performed with different animal models. Specifically, major deviations from normative neurobehavioural trajectories have been reported in animal models obtained following exposure to severe stress (maternal separation) ea rly in infancy or with rodent models of difficult and/or stressful pregnancies, including obstetric complications (e.g. prenatal restrain stress) and gestational exposure to infection (e.g prenatal immune challenge). These models have been associated with profound long-lasting deficits in the offspring's emotional and social behaviour, and with molecular changes associated with neuroplasticity.
早期身体和社会环境对终生病理表型的影响是众所周知的,现在有令人信服的证据表明,孕期或生命早期的应激经历会导致对精神疾病的易感性增强。在此,我们讨论来自临床前研究的数据,这些研究旨在调查产前或产后早期暴露于应激事件的分子后果,这些后果可能导致后期的精神病理学。特别是,我们将以使用不同动物模型进行的几项研究为例,讨论大脑成熟过程中对环境条件易受影响的年龄窗口的存在。具体而言,在婴儿期早期暴露于严重应激(母婴分离)后获得的动物模型,或在困难和/或应激妊娠的啮齿动物模型(包括产科并发症,如产前束缚应激和孕期感染,如产前免疫挑战)中,已报告与正常神经行为轨迹存在重大偏差。这些模型与后代情绪和社会行为的深刻持久缺陷以及与神经可塑性相关的分子变化有关。