Abstract
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.
Highlights
Exposure to stress during early life can have long-lasting effects, on brain function and on cognitive and emotional development, and can increase the risk of developing stress-related psychopathology in later adulthood [1,2]
A previous study showed that rat pups that were isolated individually from the dam during post-natal day (PND)7 to PND11 exhibited a deterioration in barrel cortex formation, leading to defects in whisker-dependent behaviors, while pups separated in groups did not [35]
Using c-Fos expression as a criterion for neural activity, the current authors previously found that the extended amygdala—a brain region involved in reward-seeking behavior consisting of the central nucleus of the amygdala (CeA), MePD, bed nucleus of the stria terminalis (BST), and nucleus accumbens (NAc)—was responsible for desensitization to repeated maternal separation (MS) stress during PND 1–14 [79]
Summary
Exposure to stress during early life can have long-lasting effects, on brain function and on cognitive and emotional development, and can increase the risk of developing stress-related psychopathology in later adulthood [1,2]. Most animal models that have been developed to study the outcomes of mother–infant relationship disruption have used rats to replicate the various early-life adversities to which human infants may be subjected to, with good construct and face validity. These models are related to maternal neglect [6], maternal abuse [7], repeated separations [8], and deprivation of maternal care [9], and all have resulted in immediate and/or long-term alterations of the hypothalamic–pituitary–adrenal (HPA) axis. We asked whether behavioral phenotypes are passed on to subsequent generations
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