Effects of ethanol on cultured fetal serotonergic neurons.
In utero ethanol exposure impairs the development of several neurotransmitter systems, including the serotonergic system. However, at present the mechanism by which in utero ethanol exposure damages the developing brain is unknown. This research examined the possibility that ethanol directly impairs the development of serotonergic neurons. This hypothesis was assessed by examining the content of serotonin (5-HT), 5-HT uptake, and 5-HT immunopositive neurons in cultures of fetal rhombencephalic neurons that were exposed to ethanol for 4 days in vitro. In addition, the effects of in vitro ethanol exposure on protein and DNA content of cultured rhombencephalic neurons were determined. These studies demonstrated that a 4-day exposure of cultured rhombencephalic neurons to 50 to 300 mg ethanol/dl did not affect 5-HT content, 5-HT uptake, or the proportion of 5-HT immunopositive neurons. In addition, this ethanol exposure had no significant effect on protein or DNA content. Additional studies, using a 4-day exposure to 450 mg ethanol/dl also did not detect significant differences in 5-HT uptake or in protein or DNA content. The marked differences in the findings of the present in vitro and previous in vivo studies may be due to the fact that the ethanol exposure in vivo was longer than that in vitro, and included the period of early development of serotonergic neurons and their progenitors. Alternatively, the differences may be due to ethanol-associated alterations in maternal or fetal factors (e.g., hormones, amino acids, and growth factors) that are necessary for the normal development of the serotonergic system in vivo. Normal concentrations of such factors in the serum-containing media may have protected the cultured neurons from the damaging effects of ethanol.
Lokhorst
D K
DK
Neuroscience Program, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Druse
M J
MJ
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D005333:Fetus; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012249:Rhombencephalon / Q000187:drug effects / Q000503:physiopathology; D012701:Serotonin / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D005904:Glial Fibrillary Acidic Protein; D011985:Receptors, Serotonin; D012701:Serotonin; D000431:Ethanol