Ethanol administration during early embryogenesis affects neuronal phenotypes at a time when neuroblasts are pluripotential.
Our previous studies have reported that ethanol administration during a critical period of development profoundly affects the expression of neuronal phenotypes in whole brains of chick embryos. The present study examines a) the long-lasting effects of early ethanol treatment on neurotransmitter phenotypic expression and b) its differential effects on anatomically discrete regions of the developing chick CNS. Ethanol (10 mg/50 microliters) was administered to embryos via the air sac from E1 to E3. Embryos were sacrificed on days 4, 8, 10, or 15 of embryonic development (E4, E8, E10, E15) and assayed in specific regions of the CNS for glutamate decarboxylase (GAD) or choline acetyltransferase (ChAT) as markers for GABAergic or cholinergic neurons, respectively. The magnitude of the developmental profile for ChAT was highest in spinal cord (SC), with similar profiles observed for cerebral hemispheres (CH) and optic lobes (OL). In contrast, the developmental profile for GAD was highest in OL and lowest in SC. Thus, neuronal phenotypes inhabit specific CNS areas from early primordial stages of development. Furthermore, cholinergic neuronal populations in discrete CNS areas reached mature levels by E10, whereas GABAergic populations continued to increase throughout the experimental period. We suggest that GABAergic precursor neuroblasts may differentiate at a later embryonic age and that specific regional factors may play a role in neuronal distribution and the rate of maturation. As reported previously, primordial CNS areas exposed to ethanol (E1-E3) exhibited a differential sensitivity. Cholinergic neuronal expression in CH remained retarded throughout the experimental period examined, whereas the early decline observed at E4 in SC cholinergic expression was reversed by E15.(ABSTRACT TRUNCATED AT 250 WORDS)
Kentroti
S
S
Department of Pharmacology, University of Colorado, School of Medicine, Denver 80262.
Vernadakis
A
A
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D002642:Chick Embryo; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010641:Phenotype; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D000109:Acetylcholine