Development of neurotransmitter systems in the mouse embryo following acute ethanol exposure: a histological and immunocytochemical study.
Acute maternal ethanol administration to C57B1/6J mice on gestational day 7 (GD7) results in facial and brain abnormalities similar to those reported in human fetal alcohol syndrome (FAS). Using this model, we assessed the damage to brain structures using histological methods and changes in developing neurotransmitter systems with immunocytochemistry. Cholinergic neurons in the forebrain were stained with a monoclonal antibody to choline acetyltransferase (ChAT). Catecholaminergic neurons in the midbrain and serotoninergic neurons in the hindbrain were stained with polyclonal antisera to tyrosine hydroxylase (TH) and serotonin (5-HT), respectively. Forebrain deficiencies, including loss of midline structures (olfactory bulbs, midline septation, medial septal area) and deficits in lateral and dorsal regions (neostriatum and cerebral cortex) were found in both GD14 embryos and GD18 fetuses. In severely affected offspring, complete loss of the septal region resulted in conjoined lateral ventricles and a reduction in the thickness of the ventricular zone surrounding the single ventricle, as well as a severe loss of ChAT neurons which would normally be located in this territory. However, no consistent changes were seen in the distribution or size of TH or 5-HT neuronal cell groups in the midbrain and hindbrain. These differences in effects on specific neurotransmitter systems reflect the fact that the forebrain is most severely affected by early ethanol administration, whereas the hindbrain is relatively spared. Such differential effects could produce an imbalance in developing neurotransmitter systems in the embryonic and fetal brain, which could explain some of the functional deficits observed in children with FAS.
Schambra
U B
UB
Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599-7090.
Lauder
J M
JM
Petrusz
P
P
Sulik
K K
KK
D000014:Abnormalities, Drug-Induced / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000002:abnormalities* / Q000187:drug effects / Q000473:pathology; D002795:Choline O-Acetyltransferase / Q000032:analysis; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology; D007150:Immunohistochemistry; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000473:pathology; D011247:Pregnancy; D012016:Reference Values; D012701:Serotonin / Q000032:analysis*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis*
D012701:Serotonin; D000431:Ethanol; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase