Astrocyte-mediated trophic support of developing serotonin neurons: effects of ethanol, buspirone, and S100B.
Previously, this laboratory demonstrated that the development of serotonin (5-HT) neurons and S100B-immunopositive glia proximal to these neurons is impaired in the offspring of ethanol-fed rats. However, maternal treatment with a 5-HT(1A) agonist, e.g., buspirone or ipsapirone, between gestational days 13 and 20 prevented most of the ethanol-associated changes to developing 5-HT neurons and S100B-immunopositive glia in offspring. The present in vitro studies examined the hypothesis that the protective effects of a 5-HT(1A) agonist on ethanol-exposed, developing 5-HT neurons are mediated in part by astrocyte-produced factors such as S100B. Primary cultures of fetal 5-HT neurons were maintained in conditioned medium (CM) that was obtained from ethanol- and buspirone-treated astrocytes. In order to assess the potential contribution of S100B to the protective effects of buspirone, a mouse monoclonal antibody to S100B was added to the CM to block the biological effects of this protein. These studies demonstrated that CM, obtained from ethanol-treated astrocytes, was unable to support normal development of 5-HT neurons; there was a significant reduction in the number of 5-HT neurons/well. However, CM that was obtained from astrocytes that were co-treated with buspirone and ethanol prevented the ethanol-associated reduction, and the protective effects of buspirone required S100B. We also investigated whether exogenous S100B could protect 5-HT neurons from damage caused by direct exposure to ethanol. Direct exposure of fetal brainstem neurons to ethanol in chemically-defined medium was associated with a significant reduction in the number of 5-HT immunopositive neurons/well. However, exogenous S100B protected 5-HT neurons from the ethanol-associated reduction. Our observations suggest that the protective effects of buspirone on ethanol-exposed, developing 5-HT neurons are mediated in part by the astrocyte-produced factor S100B.
Eriksen
J L
JL
The Neuroscience Program and Division of Molecular & Cellular Biochemistry, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA.
Druse
M J
MJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002065:Buspirone / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D009414:Nerve Growth Factors / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D002135:Calcium-Binding Proteins; D002492:Central Nervous System Depressants; D017077:Culture Media, Conditioned; D009414:Nerve Growth Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579159:S100b protein, mouse; C579158:S100b protein, rat; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol; D002065:Buspirone