Effects of early life adverse experiences on the brain: implications from maternal separation models in rodents.

Mayumi Nishi,Takayo Sasagawa,Noriko Horii-Hayashi

doi:10.3389/fnins.2014.00166

Abstract

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.

Highlights

As our contemporary society changes rapidly, changes in family structure can have a large influence on the mother–child relationship, as well as on other social environmental factors
SERUM LEVEL OF CORT In rodents, there is an unique period during which the HPA axis shows a rapid regression known as the stress hyporesponsive period (SHRP) (Levine, 2001)
We reported that repeated maternal separation (MS) for 3 h daily from PND1 to PND14 did not elevate a baseline level of CORT on PND14, whereas a single-time MS for 3 h at PND14 raised a baseline CORT level (Figure 1) (Horii-Hayashi et al, 2013)

Summary

INTRODUCTION

As our contemporary society changes rapidly, changes in family structure can have a large influence on the mother–child relationship, as well as on other social environmental factors. EARLY MS The inventive studies of Levine and colleagues, and of Meaney, Plotsky, and their collaborators have demonstrated that changes in rodents’ early postnatal experiences can induce profound long-lasting effects on emotionality and stress response (Levine, 1967; Meaney, 2001; Plotsky et al, 2005), which have spurred the employment of the rodent MS for investigating early life stress This early life stress model is based on the evidence that unfavorable events in early life cause the vulnerability for developing various kinds of diseases in later life. Miyazaki and colleagues recently reported that rat pups isolated singly from the mother during PND7 to PND11 presented disturbance of cortical function, whereas pups separated but gathered from PND7 to PND11 showed no cortical disruption (Miyazaki et al, 2012)

CHARACTERIZATION OF MATERNALLY SEPARATED ANIMALS

CONCLUSIONS