Dept. of Psychology and Center "Daniel Bovet", Sapienza University, 00184, Rome, Italy; IRCCS Fondazione Santa Lucia, Via Del Fosso di Fiorano, 64, 00143, Rome, Italy.
Dept. of Psychology and Center "Daniel Bovet", Sapienza University, 00184, Rome, Italy; IRCCS Fondazione Santa Lucia, Via Del Fosso di Fiorano, 64, 00143, Rome, Italy.
Mol Cell Endocrinol. 2021 Feb 5;521:111125. doi: 10.1016/j.mce.2020.111125. Epub 2020 Dec 15.
Adaptation to environmental challenges represents a critical process for survival, requiring the complex integration of information derived from both external cues and internal signals regarding current conditions and previous experiences. The Hypothalamic-pituitary-adrenal axis plays a central role in this process inducing the activation of a neuroendocrine signaling cascade that affects the delicate balance of activity and cross-talk between areas that are involved in sensorial, emotional, and cognitive processing such as the hippocampus, amygdala, Prefrontal Cortex, Ventral Tegmental Area, and dorsal raphe. Early life stress, especially early critical experiences with caregivers, influences the functional and structural organization of these areas, affects these processes in a long-lasting manner and may result in long-term maladaptive and psychopathological outcomes, depending on the complex interaction between genetic and environmental factors. This review summarizes the results of studies that have modeled this early postnatal stress in rodents during the first 2 postnatal weeks, focusing on the long-term effects on molecular and structural alteration in brain areas involved in Hypothalamic-pituitary-adrenal axis function. Moreover, a brief investigation of epigenetic mechanisms and specific genetic targets mediating the long-term effects of these early environmental manipulations and at the basis of differential neurobiological and behavioral effects during adulthood is provided.
适应环境挑战是生存的关键过程，需要复杂地整合来自外部线索和关于当前条件和以往经验的内部信号的信息。下丘脑-垂体-肾上腺轴在这个过程中起着核心作用，它诱导神经内分泌信号级联的激活，影响参与感觉、情感和认知处理的区域之间的微妙平衡，如海马体、杏仁核、前额叶皮层、腹侧被盖区和中缝背核。早期生活压力，特别是与照顾者的早期关键经历，影响这些区域的功能和结构组织，以持久的方式影响这些过程，并可能导致长期适应不良和精神病理结果，这取决于遗传和环境因素之间的复杂相互作用。这篇综述总结了在啮齿动物中模拟出生后前 2 周早期压力的研究结果，重点关注对涉及下丘脑-垂体-肾上腺轴功能的大脑区域的分子和结构改变的长期影响。此外，还简要探讨了介导这些早期环境操作的长期影响的表观遗传机制和特定遗传靶点，以及成年期不同神经生物学和行为效应的基础。
