Department of Anatomy and Cell Biology, Nara Medical University, Kashihara 634-8521, Japan.
Int J Mol Sci. 2020 Sep 29;21(19):7212. doi: 10.3390/ijms21197212.
Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic-pituitary-adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity-focusing on serum corticosterone (CORT)-and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.
生命早期的产前和产后压力会影响影响大脑功能的神经网络的形成。先前的研究表明，母体分离（MS）是一种典型的啮齿动物模型，相当于生命早期的压力，更具体地说，相当于人类的虐待和/或忽视，可以调节下丘脑-垂体-肾上腺（HPA）轴，影响随后的神经元功能和情绪行为。然而，生命早期压力对大脑功能的持久影响的神经基础尚不清楚。在本综述中，我们描述了 HPA 轴活性的改变，重点是血清皮质酮（CORT）以及 HPA 轴的终产物和 CORT 受体在啮齿动物中的改变。然后，我们通过研究 c-Fos 表达，介绍了在各种 MS 模式下激活的脑区，包括在断奶前的不同阶段重复 MS 和单次暴露于 MS，c-Fos 表达是神经元活动的生物学标志物。此外，我们讨论了 MS 暴露的成年小鼠的行为和大脑中基因表达的改变。最后，我们询问 MS 是否会重复发生，以及虐待和忽视是否可以在代际之间传递。
