Exposure of neonatal rats to alcohol by vapor inhalation demonstrates specificity of microcephaly and Purkinje cell loss but not astrogliosis.
The artificial rearing model (AR) of fetal alcohol syndrome (FAS) has been shown to induce several major pathologies in the early postnatal rat brain development: microcephaly, selective neuronal cell loss, and activation of astroglia in the neocortex. The purpose of this study was to determine whether these pathologies were specific to the action of alcohol or, in contrast, could result from confounds attributed to this model of FAS. For this purpose, the pathological effects of AR were compared with those of a vapor inhalation (VI) model of FAS. Our studies showed that the microcephaly that developed after exposure to periodic blood alcohol levels (BALs) of 300-350 mg% during postnatal days 4-9 could be achieved by both AR and IV models of FAS, and thus is independent of the method of alcohol administration. In contrast, the gliosis measured by glial fibrillary acidic protein (GFAP) mRNA levels in cortex, as well as by immunohistochemical staining for GFAP, was found only in the AR-FAS model, but not in the VI model. However, the lack of gliosis in VI was apparently not due to a less intrusive intervention of alcohol, because VI exposure resulted in a reduction in Purkinje cell number comparable with that found after AR or intragastric intubation of alcohol. Based on these observations, we conclude that the activation of gliosis observed after AR is not a specific effect of alcohol, but rather is caused by an interaction of alcohol with as yet unidentified factors present in AR.
Ryabinin
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Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Cole
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M
Bloom
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FE
Wilson
M C
MC
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000473:pathology*; D002452:Cell Count / Q000187:drug effects; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology*; D008297:Male; D008831:Microcephaly / Q000473:pathology*; D011247:Pregnancy; D011689:Purkinje Cells / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005904:Glial Fibrillary Acidic Protein; D000431:Ethanol