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Open Access Highly Accessed Research article

Pre-gestational stress reduces the ratio of 5-HIAA to 5-HT and the expression of 5-HT1A receptor and serotonin transporter in the brain of foetal rat

Yuejun Huang1, Hongwu Xu2, Hui Li3, Hanhua Yang1, Yunbin Chen4* and Xuechuan Shi1*

Author Affiliations

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

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

3 Mental Health Center of Shantou University, Tai Shan Rd, Shantou 515041, Guangdong, China

4 Maternal and Child Health Hospital of Guangdong Province, West Guangyuan Rd, GuangZhou 510010, Guangdong, China

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BMC Neuroscience 2012, 13:22  doi:10.1186/1471-2202-13-22

Published: 28 February 2012

Abstract

Background

Many studies have found that stress before or during pregnancy is linked to an increased incidence of behavioural disorders in offspring. However, few studies have investigated hypothalamic-pituitary-adrenal (HPA) axis activity and the serotonergic system as a consequence of pregestational stress. In the present study, we investigated the effect of pre-gestational stress on HPA axis activity in maternal rats and their foetuses and examined whether changes in HPA axis activity of maternal rats produced functional changes in the serotonergic system in the brain of foetuses.

Results

We used the behavioural tests to assess the model of chronic unpredictable stress (CUS) in maternal rats. We found the activity in the open field and sucrose consumption was lower for rats with CUS than for the controls. Body weight but not brain weight was higher for control foetuses than those from the CUS group. Serum corticosterone and corticotrophin-releasing hormone levels were significantly higher for mothers with CUS before pregnancy and their foetuses than for the controls. Levels of 5-hydroxytryptamine (5-HT) were higher in the hippocampus and hypothalamus of foetuses in the CUS group than in the controls, and 5-hydroxyindoleacetic acid (5-HIAA) levels were lower in the hippocampus in foetuses in the CUS group than in the control group. Levels of 5-HIAA in the hypothalamus did not differ between foetuses in the CUS group and in the control group. The ratio of 5-HIAA to 5-HT was significantly lower for foetuses in the CUS group than in the control group. Levels of 5-HT1A receptor were significantly lower in the foetal hippocampus in the CUS group than in the control group, with no significant difference in the hypothalamus. The levels of serotonin transporter (SERT) were lower in both the foetal hippocampus and foetal hypothalamus in the CUS group than in the control group.

Conclusions

Our data demonstrate that pre-gestational stress alters HPA axis activity in maternal rats and their foetuses, which is associated with functional changes in 5-HT activity (5-HT, 5-HIAA and ratio of 5-HIAA to 5-HT), as well as the levels of the 5-HT1A receptor and SERT in the hippocampus and hypothalamus of foetuses.

Keywords:
Corticosterone; HPA axis; Serotonin; Serotonin transporter; Stress