The serotonin-1A agonist ipsapirone prevents ethanol-associated death of total rhombencephalic neurons and prevents the reduction of fetal serotonin neurons.
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.
Druse
Mary J
MJ
Division of Molecular and Cellular Biochemistry, Loyola University, Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153, USA. mmanteu@lumc.edu
Tajuddin
Nuzhath F
NF
Gillespie
Roberta A
RA
Dickson
Elizabeth
E
Atieh
Mohammed
M
Pietrzak
Constance A
CA
Le
Phong T
PT
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
D002492:Central Nervous System Depressants; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000431:Ethanol; C043077:ipsapirone