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Open Access Highly Accessed Research article

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

Yuejun Huang12, Sihong Chen2, Hongwu Xu13, Xiaochan Yu2, Huihong Lai2, Guyu Ho2, Qingjun Huang4* and Xuechuan Shi12*

Author Affiliations

1 Transforming Medical Center, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou, Guangdong 515041, China

2 Department of Pediatrics, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou, Guangdong 515041, China

3 Department of Neurosurgery, Second Affiliated Hospital of Medical College of Shantou University, North Dongxia Rd, Shantou, Guangdong 515041, China

4 Joint Lab of Biological Psychiatry, Mental Health Center of Shantou University, Taishan Rd, Shantou, Guangdong 515041, China

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BMC Neuroscience 2013, 14:67  doi:10.1186/1471-2202-14-67

Published: 8 July 2013

Abstract

Background

There 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.

Results

We 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.

Conclusion

Our 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.

Keywords:
Stress; Dopamine; Medial prefrontal cortex; Dopamine transporter; Norepinephrine transporter; Catechol-O-methyltransferase