title: The effect of ethanol chronically administered to preweanling rats on cerebellar development: a morphological study.
abstract: The effects of ethanol on body, brain and cerebellar growth of the postnatal rat have been studied. Vapor inhalation, the procedure used to administer ethanol directly to preweanling (3-20-day-old) rats, produced maximal blood ethanol levels that averaged 239 mg/100 ml. Weight determinations indicated that brain but not body growth was significantly stunted by exposure to ethanol. Moreover, cerebellar growth, which occurred largely but not wholly during the period of ethanol treatment, was inhibited twice as much as the rest of the brain. Arrested brain and cerebellar growth appeared shortly after ethanol treatment was begun and persisted into adulthood following a postweaning rehabilitation period. Ethanol treatment diminished the growth of both the anterior and posterior lobes and of all layers of the cerebellar vermis. However, the effect of ethanol was larger in the anterior lobe than the posterior lobe, and the medullary layer was more retarded than the others. Some compensatory growth occurred in the molecular and granular layers of the experimental rats during a postweaning rehabilitation period. The effects of ethanol on 2 major neuronal populations of the cerebellar cortex -- the large, prenatally-formed Purkinje cells and the small, postnatally-formed granule cells -- were assessed via light microscopy. After 2 days of ethanol treatment the number of Purkinje cells in all 10 vermal lobules was reduced; neither additional exposure to ethanol nor a postweaning rehabilitation period subsequently altered cell number. The possibility that the regional magnitude of the Purkinje cell loss was related to the chronology of lobular development was discussed; Purkinje cells in the latest maturing lobules being least affected. The morphological development of surviving Purkinje cells proceeded normally. An autoradiographic study indicated the pattern of granule cell neurogenesis in cerebella of ethanol-treated rats and of control rats did not differ, although the experimental animals had consistently fewer cells in all stages of development. The ultimate loss of 20-25% of their granule cells was accounted for by an early diminution of the stem cell population of the external germinal layer by about 10%. The results suggest the initial targets of ethanol were the immature Purkinje cells, which were reduced in number before the onset of granule cell formation. A complex age-dependent interaction between blood ethanol levels and vulnerable periods in Purkinje cell development was suggested. Mechanisms for the subsequent correlative reduction in the granule cell population were also discussed.
mesh_terms: D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002452:Cell Count; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011689:Purkinje Cells / Q000473:pathology; D051381:Rats
chemical_list: D000431:Ethanol