Pre-gestational stress alters stress-response of pubertal offspring rat in sexually dimorphic and hemispherically asymmetric manner

Yuejun Huang,Hongwu Xu,Qingjun Huang,Huihong Lai,Sihong Chen,Xiaochan Yu,Xuechuan Shi,Guyu Ho

doi:10.1186/1471-2202-14-67

Abstract

BackgroundThere is increasing evidence that maternal stress may have long-term effects on brain development in the offspring. In this study, we examined whether pre-gestational stress might affect offspring rats on the medial prefrontal cortical (mPFC) dopaminergic activity in response to acute stress in puberty and if so, whether such effects exhibited hemispheric asymmetry or sexual dimorphism.ResultsWe used behavioral tests to assess the model of chronic unpredictable stress (CUS). We found that the activity in the open field test and sucrose intake test were lower for maternal rats in the CUS group than those in the control group. Offspring rats in the CUS group floated more and swam or climbed less as compared to the offsprings in the control group in the forced swimming test. The floating time was longer and swimming or climbing time was shorter in the female offspring rats than those in the males. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for CUS maternal rats and their offsprings than the respective controls. The ratio of dihydroxy-phenyl acetic acid (DOPAC) to dopamine (DA), DA transporter (DAT), norepinephrine transporter (NET) were lower in the mPFC of offspring rats in the CUS group than the control group. Levels of catechol-O-methyltransferase (COMT) in the left mPFC of female offspring rats and in the right mPFC of both female and male offspring rats were lower in the CUS group than those in the controls, but there was no difference in the left mPFC of male offspring between the CUS and control groups. DOPAC, the ratio of DOPAC to DA, NET and COMT were lower in the right mPFC than in the left mPFC of offspring rats in the CUS group. The ratio of DOPAC to DA in the right mPFC was lower in the female offspring rats than male offspring rats in the CUS group. The NET and COMT levels in both left and right mPFC were lower in the female offspring rats than those of the male offsprings in the CUS group.ConclusionOur data provide evidence that the effect of pre-gestational stress on the mPFC dopaminergic activity in response to acute stress exhibited hemispheric asymmetry and sexual dimorphism in the pubertal offspring rats.

Highlights

There is increasing evidence that maternal stress may have long-term effects on brain development in the offspring
Covariance analysis on the OFT after chronic unpredictable stress (CUS) as the dependent variable and group as the fixed factor and the results of OFT before CUS as covariate revealed that the moving behaviour of maternal rats in the CUS group was decreased significantly compared to the control group at week 3 [total arena: F(1,18) = 42.983, P < 0.001; peripheral arena: F(1,18) = 36.616, P < 0.001; central arena: F(1,18) = 4.921, P = 0.046] (Figure 2B)
Levels of COMT in the left medial prefrontal cortical (mPFC) of female offspring rats in the CUS group were lower than those in the control group [F(1,52) = 41.872, P < 0.001], but there was no difference in the left mPFC of male offspring between the CUS group and the control group [F(1,52) = 0.783, P = 0.38]

Summary

Introduction

There is increasing evidence that maternal stress may have long-term effects on brain development in the offspring. We examined whether pre-gestational stress might affect offspring rats on the medial prefrontal cortical (mPFC) dopaminergic activity in response to acute stress in puberty and if so, whether such effects exhibited hemispheric asymmetry or sexual dimorphism. The most extensively studied system susceptible to stress is the hypothalamus–pituitary–adrenal (HPA) axis This neuroendocrine axis regulates a variety of metabolic processes by secreting glucocorticoids (GCs) in response to stress [4,5]. The development of such hemispheric asymmetries in mPFC can be altered by perinatal factors [21] These findings, along with the evidence derived from clinical observations, have led to the suggestion that abnormal lateralisation of mPFC DA-mediated function may increase the vulnerability to a range of stress-related psychopathologies [22]

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Discussion

Conclusion