title: The serotonin-1A agonist ipsapirone prevents ethanol-associated death of total rhombencephalic neurons and prevents the reduction of fetal serotonin neurons.
abstract: Previously, this laboratory showed that in utero and in vitro ethanol exposure significantly reduces developing serotonin (5-HT) neurons and that treatment with a 5-HT1A agonist such as buspirone or ipsapirone prevents the ethanol-associated loss. The present study investigated whether ethanol decreases fetal rhombencephalic neurons, including 5-HT neurons, by causing apoptosis. We also investigated whether ipsapirone prevents the ethanol-associated deficit of fetal rhombencephalic neurons by reducing apoptosis. The results of these studies strongly suggest that the ethanol-associated reduction in fetal rhombencephalic neurons that accompanies both in utero and in vitro exposure to physiological concentrations of ethanol is associated with increased apoptosis in these neurons. A physiological concentration of ethanol (i.e., 50 mM) increases apoptosis in fetal rhombencephalic neurons and decreases the number 5-HT neurons. It also appears that the 5-HT1A agonist ipsapirone provides neuroprotection to these neurons by reducing apoptosis. Another mechanism by which ethanol-associated apoptosis can be blocked is by including serum proteins in the media at a concentration of 1% or higher; this concentration of serum proteins is high in comparison to the protein concentration in cerebrospinal fluid.
authors.affiliation: Division of Molecular and Cellular Biochemistry, Loyola University, Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. mmanteu@lumc.edu
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Druse
authors.forename: Nuzhath F
authors.initials: NF
authors.lastname: Tajuddin
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Gillespie
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dickson
authors.forename: Mohammed
authors.initials: M
authors.lastname: Atieh
authors.forename: Constance A
authors.initials: CA
authors.lastname: Pietrzak
authors.forename: Phong T
authors.initials: PT
authors.lastname: Le
mesh_terms: D000367:Age Factors; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling / Q000379:methods; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000166:cytology*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol; C043077:ipsapirone