Neonatal ethanol exposure alters bcl-2 family mRNA levels in the rat cerebellar vermis

Background: The objective of the present work was to determine whether etha nol-induced cerebellar cell death during development is related to alterati ons in the expression of bcl-2 family genes. Methods: Rats were exposed to ethanol or control conditions during the neon atal period and transcript levels of bcl-2 family members relative to cyclo philin were determined. Pups exposed in parallel were taken for cerebellar cell counts. Results: Ethanol exposure during the first postnatal week significantly red uced Purkinje and granule cell numbers by postnatal day 21 (P21). Acute fir st postnatal week ethanol exposure up-regulated mRNA transcripts encoding t he cell death-promoting molecules bar and bcl-xs as measured on P4. An addi tional day of exposure on P5 resulted in no further alterations in bcl-2 fa mily transcripts, likely because Purkinje cell death was detectable as earl y as P5. To determine whether proapoptotic gene expression changes were spe cific to first postnatal week ethanol neurotoxicity, we examined bcl-2 fami ly mRNA levels in rats exposed to ethanol during a developmental period of cerebellar insusceptibility, the second postnatal week. Exposure on P7 to P 8 produced no change in cerebellar cell number, but also resulted in increa sed levels of bar, although only after 2-day ethanol exposure and not after acute exposure on P7. Conclusions: These data implicate altered expression of proapoptotic member s of the bcl-2 gene family in acute ethanol-mediated cerebellar cell death during the first postnatal week. They also suggest that the differential su rvival of cerebellar neurons after ethanol exposure during more mature deve lopmental stages may be related to more successful suppression of proapopto tic processes.