GABA attenuates the neurotoxic effects of ethanol in neuron-enriched cultures from 8-day-old chick embryo cerebral hemispheres.
Neuron-enriched cultures were prepared from 8-day-old chick embryo cerebral hemispheres and exposed to ethanol (50 mM), GABA (10(-5) M) and ethanol (50 mM) + GABA (10(-5) M) from day 4 to 8 in culture. At day 8, control, ethanol, GABA and ethanol + GABA-treated cultures were examined morphologically and biochemically. Choline acetyltransferase (ChAT) and glutamic acid decarboxylase (GAD) activities were used as markers for cholinergic and GABAergic neuronal phenotypic expression, respectively. Control cultures showed more numerous and large neuronal aggregates as well as prominent neuritic bundles. Moreover, cultures treated with GABA depicted even more numerous neuronal aggregates with interconnecting neurites as compared to control. In contrast, ethanol-treated cultures exhibited smaller neuronal aggregates with less prominent neuritic bundles than control. However, cultures treated concomitantly with ethanol + GABA exhibited numerous and larger aggregates than cultures treated with ethanol alone. Neuritic bundles which were highly reduced in ethanol-treated cultures became prominent in the presence of GABA. As previously reported, ethanol alone enhanced ChAT and reduced GAD activities. GABA given alone enhanced the expression of both neuronal phenotypes. When GABA was given concomitantly with ethanol the decline in GAD and the rise in ChAT observed in ethanol-treated cultures was restored by GABA to almost control levels. Thus, ethanol-induced alterations in morphology and neuronal phenotypes were counteracted by the neurontrophic effect of GABA.
Spoerri
P E
PE
Department of Psychiatry, University of Colorado, Denver 80262, USA.
Srivastava
N
N
Vernadakis
A
A
D000818:Animals; D001921:Brain / Q000196:embryology*; D002478:Cells, Cultured; D002642:Chick Embryo; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D009498:Neurotoxins; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase