Prenatal Alcohol Exposure Results in Long-Term Serotonin Neuron Deficits in Female Rats: Modulatory Role of Ovarian Steroids

Authors

  • Joanna H. Sliwowska,

    Corresponding author
    1. Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
    2. Laboratory of Neurobiology , Institute of Zoology, Poznan University of Life Sciences, Poznan, Poland
    • Reprint requests: Joanna H. Sliwowska, PhD, Laboratory of Neurobiology, Institute of Zoology, Poznan University of Life Sciences, ul. Wojska Polskiego 71C, 60-625 Poznan, Poland; Tel.:+48 61 848 7866; Fax: +48 61 848 7650; E-mail: joanna.sliwowska@gmail.com

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  • Hyun Jung Song,

    1. Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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  • Tamara Bodnar,

    1. Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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  • Joanne Weinberg

    1. Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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Abstract

Background

Previous studies on male rodents found that prenatal alcohol exposure (PAE) decreases the number of serotonin immunoreactive (5-HT-ir) neurons in the brainstem. However, data on the effects of PAE in females are lacking. In light of known sex differences in responsiveness of the 5-HT system and known effects of estrogen (E2) and progesterone (P4) in the brain, we hypothesized that sex steroids will modulate the adverse effects of PAE on 5-HT neurons in adult females.

Methods

Adult females from 3 prenatal groups (Prenatal alcohol-exposed [PAE], Pair-fed [PF], and ad libitum-fed Controls [C]) were ovariectomized (OVX), with or without hormone replacement, or underwent Sham OVX. 5-HT-ir cells were examined in key brainstem areas.

Results

Our data support the hypothesis that PAE has long-term effects on the 5-HT system of females and that ovarian steroids have a modulatory role in these effects. Intact (Sham OVX) PAE females had marginally lower numbers of 5-HT-ir neurons in the dorsal raphe nucleus of the brainstem compared with PF and C females. This marginal difference became significant following removal of hormones by OVX. Replacement with E2 restored the number of 5-HT-ir neurons in PAE females to control levels, while P4 reversed the effects of E2. Importantly, despite these differential responses of the 5-HT system to ovarian steroids, there were no differences in E2 and P4 levels among prenatal treatment groups.

Conclusions

These data demonstrate long-term, adverse effects of PAE on the 5-HT system of females, as well as differential sensitivity of PAE compared with control females to the modulatory effects of ovarian steroids on 5-HT neurons. Our findings have important implications for understanding sex differences in 5-HT dysfunction in depression/anxiety disorders and the higher rates of these mental health problems in individuals with fetal alcohol spectrum disorder.

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