Department of Anatomy and Cell Biology, Nara Medical University Kashihara, Japan.
Front Neurosci. 2014 Jun 17;8:166. doi: 10.3389/fnins.2014.00166. eCollection 2014.
During postnatal development, adverse early life experiences affect the formation of neuronal networks and exert long-lasting effects on neural function. Many studies have shown that daily repeated maternal separation (MS), an animal model of early life stress, can regulate the hypothalamic-pituitary-adrenal axis (HPA axis) and affect subsequent brain function and behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been fully elucidated. In this mini review, we present various cases of MS in rodents and illustrate the alterations in HPA axis activity by focusing on corticosterone (CORT). We then show a characterization of the brain regions affected by various patterns of MS, including repeated MS and single time MS at various stages before weaning, by investigating c-Fos expression. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Next, we introduce how early life stress can impact behavior, namely by inducing depression, anxiety or eating disorders, and alterations in gene expression in adult mice subjected to MS.
在出生后发育过程中，不良的早期生活经历会影响神经网络的形成，并对神经功能产生持久影响。许多研究表明，每日重复的母体分离（MS），即一种早期生活应激的动物模型，可以调节下丘脑-垂体-肾上腺轴（HPA 轴），并影响成年期以后的大脑功能和行为。然而，早期生活应激对大脑功能的持久影响的分子基础尚未完全阐明。在这篇迷你综述中，我们介绍了啮齿动物的各种 MS 情况，并通过关注皮质酮（CORT）来阐明 HPA 轴活性的改变。然后，我们通过研究 c-Fos 表达，展示了各种 MS 模式（包括在断奶前的不同阶段重复 MS 和单次 MS）对大脑区域的影响特征。这些 CORT 和 c-Fos 研究表明，反复的早期生活应激可能以区域和时间特异性的方式影响神经元功能，表明对早期生活应激的习惯化存在关键时期。接下来，我们介绍了早期生活应激如何影响行为，即通过诱导抑郁、焦虑或饮食失调，以及 MS 后成年小鼠的基因表达改变。
