Roque Angélica, Valles Méndez Kinberli Marcela, Ruiz Roberto, Pineda Edel, Lajud Naima
Laboratorio de Neurobiología del Desarrollo, División de Neurociencias, Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, Morelia, México.
Eur J Neurosci. 2022 May;55(9-10):2108-2121. doi: 10.1111/ejn.15193. Epub 2021 Mar 26.
Early life stress (ELS) programs hypothalamus-pituitary-adrenal (HPA) axis activity and affects synaptic plasticity and cognitive performance in adults; however, the effects of ELS during the temporal window of vulnerability are poorly understood. This study aimed to thoroughly characterize the effects of ELS in the form of periodic maternal separation (MS180) during the time of exposure to stress. Hippocampal corticotropin-releasing hormone (CRH) gene expression and baseline HPA axis activity were analyzed at postnatal (P) days 6, 12, 15, and 21, and in adulthood (P75); these factors were correlated with plasticity markers and adult behavior. Our results indicate that MS180 induces an increase in hippocampal CRH expression at P9, P12, and P15, whereas an increase in hypothalamic CRH expression was observed from P12 to P21. Increased arginine-vasopressin expression and corticosterone levels were observed only at P21. Moreover, MS180 caused transient alterations in hypothalamic synaptophysin expression during early life. As adults, MS180 rats showed a passive coping strategy in the forced swimming test, cognitive impairments in the object location test, increased hypothalamic CRH expression, and decreased oxytocin (OXT) expression. Spearman's analysis indicated that cognitive impairments correlated with CRH and OXT expression. In conclusion, our data indicate that MS180 induces a transient increase in hippocampal CRH expression in neonates that precedes the effects on hypothalamic neuropeptides, confirming the role of increased CRH during the temporal window of vulnerability as a mediator of some of the detrimental effects of ELS on brain development and adult behavior.
早年生活应激（ELS）会调节下丘脑 - 垂体 - 肾上腺（HPA）轴的活动，并影响成年人的突触可塑性和认知表现；然而，在易损期的ELS影响却知之甚少。本研究旨在全面描述以周期性母婴分离（MS180）形式存在的ELS在应激暴露期间的影响。在出生后（P）第6、12、15和21天以及成年期（P75）分析海马促肾上腺皮质激素释放激素（CRH）基因表达和基线HPA轴活动；这些因素与可塑性标志物和成年行为相关。我们的结果表明，MS180在P9、P12和P15时诱导海马CRH表达增加，而从P12到P21观察到下丘脑CRH表达增加。仅在P21时观察到精氨酸加压素表达和皮质酮水平升高。此外，MS180在生命早期导致下丘脑突触素表达的短暂改变。成年后，MS180大鼠在强迫游泳试验中表现出被动应对策略，在物体定位试验中存在认知障碍，下丘脑CRH表达增加，催产素（OXT）表达减少。Spearman分析表明，认知障碍与CRH和OXT表达相关。总之，我们的数据表明，MS180在新生儿中诱导海马CRH表达短暂增加，这先于对下丘脑神经肽的影响，证实了在易损期CRH增加作为ELS对大脑发育和成年行为的一些有害影响的介质的作用。
