Alcohol exposure on postnatal day 5 induces Purkinje cell loss and evidence of Purkinje cell degradation in lobule I of rat cerebellum.
The reduction in neuron number in specific brain regions is one of the most destructive aspects of alcohol-induced developmental brain injury, and its occurrence depends on the timing, pattern, and dose of maternal alcohol consumption during pregnancy. The purpose of this investigation was to quantify the dose-response aspect of Purkinje cell loss and rapid cellular degradation indicative of Purkinje cell loss following a single alcohol exposure on postnatal day 5 in lobule I, a lobule that has been shown to be vulnerable to alcohol-induced injury during cerebellar development. Fluoro-Jade B was used to identify Purkinje cell degeneration in 2-h intervals during the first 24h following the single alcohol exposure. At the end of 24h, stereology cell counting techniques were used to estimate the number of Purkinje cells in lobule I of the cerebellum. Significant Fluoro-Jade B labeling of lobule I Purkinje cells began at 12-h postexposure in the 6.0-g/kg group with continued significant expression of the marker at the 16- and 18-h time points. Notably, the magnitude of Fluoro-Jade B expression in the 6.0-g/kg group remained high during the period between 12 and 24h even though the difference between the 6.0-g/kg group and other groups did not reach statistical significance at the 14-, 20-, and 24-h time points. On postnatal day 6, 24h following the alcohol exposure, rats exposed to the highest alcohol dose (6.0 g/kg) had lost significantly more Purkinje cells than those in the nutritional or caloric control to the highest dose of alcohol group. These results are suggestive of a unique relationship among the quantity of alcohol, the onset and duration of cell degradation, and the degree of eventual cell loss. Given that cerebellar Purkinje cells (and many developing neurons) are vulnerable to alcohol-induced neuronal loss within hours of a single alcohol insult, women should be counseled to avoid drinking alcohol in a manner that significantly increases blood alcohol levels during pregnancy (e.g., binge drinking).
Lee
Youngki
Y
Department of Histology, College of Medicine, Cheju National University, Jeju-si-690-756, Republic of Korea.
Rowe
Julie
J
Eskue
Kyle
K
West
James R
JR
Maier
Susan E
SE
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D016923:Cell Death; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008297:Male; D008856:Microscopy, Fluorescence; D009929:Organ Size; D009930:Organic Chemicals; D011689:Purkinje Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015430:Weight Gain
D002492:Central Nervous System Depressants; D005452:Fluoresceins; D005456:Fluorescent Dyes; D009930:Organic Chemicals; C435731:fluoro jade; D000431:Ethanol