Astrocyte-mediated trophic support of developing serotonin neurons: effects of ethanol, buspirone, and S100B

Brain Res Dev Brain Res. 2001 Nov 26;131(1-2):9-15. doi: 10.1016/s0165-3806(01)00240-1.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Buspirone / pharmacology*
  • Calcium-Binding Proteins / immunology
  • Calcium-Binding Proteins / metabolism*
  • Cell Communication / drug effects
  • Cells, Cultured
  • Central Nervous System Depressants / pharmacology*
  • Culture Media, Conditioned / pharmacology
  • Ethanol / pharmacology*
  • Female
  • Nerve Growth Factors / immunology
  • Nerve Growth Factors / metabolism*
  • Neurons / cytology
  • Neurons / physiology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins*
  • Serotonin / physiology
  • Serotonin Receptor Agonists / pharmacology*


  • Antibodies, Monoclonal
  • Calcium-Binding Proteins
  • Central Nervous System Depressants
  • Culture Media, Conditioned
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • S100b protein, mouse
  • S100b protein, rat
  • Serotonin Receptor Agonists
  • Serotonin
  • Ethanol
  • Buspirone