title: Prenatal alcohol exposure results in long-term serotonin neuron deficits in female rats: modulatory role of ovarian steroids.
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.
authors.affiliation: Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Laboratory of Neurobiology , Institute of Zoology, Poznan University of Life Sciences, Poznan, Poland.
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Sliwowska
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Song
authors.forename: Tamara
authors.initials: T
authors.lastname: Bodnar
authors.forename: Joanne
authors.initials: J
authors.lastname: Weinberg
mesh_terms: D000818:Animals; D004958:Estradiol / Q000494:pharmacology / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D020249:Hormone Replacement Therapy / Q000379:methods; D008297:Male; D010052:Ovariectomy; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D000431:Ethanol; D011374:Progesterone; D004958:Estradiol
keywords: Estradiol; Ethanol; Prenatal Alcohol Exposure; Progesterone; Serotonin (5-HT)
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