title: Effects of in utero ethanol exposure and maternal treatment with a 5-HT(1A) agonist on S100B-containing glial cells.
abstract: This laboratory previously showed that in utero ethanol exposure severely impairs the development of the cell bodies and projections of serotonin (5-HT) neurons, and that maternal treatment with a 5-HT(1A) agonist prevents many of these abnormalities. Others demonstrated that stimulation of fetal astroglial 5-HT(1A) receptors increases production and release of S100B, a glial trophic factor that is essential for the development of 5-HT neurons. The present study investigated a potential mechanism by which ethanol hinders development of 5-HT neurons, and by which maternal 5-HT(1A) agonist treatment prevents this damage. This study tested the hypothesis that in utero ethanol exposure reduces the number of S100B immunopositive glia and that maternal 5-HT(1A) agonist treatment prevents ethanol-associated changes in S100B. To test our hypothesis, we determined the effects of in utero ethanol exposure and maternal treatments with the 5-HT(1A) agonists ipsapirone and buspirone on S100B immunopositive glial cells. On gestation day 20 (G20), S100B immunopositive cells were quantified in the midline raphe glial structure (MRGS), a large transient structure that contains substantial numbers of S100B-positive glial cells and that spans the dorsal raphe, median raphe, and B9 complex of 5-HT neurons. S100B immunopositive glial cells were also determined in an area proximal to the dorsal raphe in postnatal day 2 (PN2) rats. In utero ethanol exposure significantly reduced S100B immunopositive glial cells in the MRGS at G20 and in the dorsal raphe at PN2. In addition, treatment of pregnant rats with a 5-HT(1A) agonist between G13 and G20 prevented the ethanol-associated reduction in S100B immunopositive glial cells. These studies demonstrated that part of ethanol's damaging effects on developing 5-HT neurons is mediated by a reduction of S100B and that some of the protective effects of maternal 5-HT(1A) agonist treatment are related to the actions of these drugs on glial cells.
authors.affiliation: The Neuroscience Program, Loyola University Stritch School of Medicine, 60153, Maywood, IL, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Eriksen
authors.forename: R A
authors.initials: RA
authors.lastname: Gillespie
authors.forename: M J
authors.initials: MJ
authors.lastname: Druse
mesh_terms: D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics*; D002452:Cell Count / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000188:drug therapy / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics*; D009457:Neuroglia / Q000737:chemistry / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011903:Raphe Nuclei / Q000002:abnormalities / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
chemical_list: D002135:Calcium-Binding Proteins; D002492:Central Nervous System Depressants; D009414:Nerve Growth Factors; D011743:Pyrimidines; D012333:RNA, Messenger; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579158:S100b protein, rat; D017366:Serotonin Receptor Agonists; D000431:Ethanol; C043077:ipsapirone; D002065:Buspirone