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 ethanol-induced cerebellar cell death during development is related to alterations in the expression of bcl-2 family genes. Methods: Rats were exposed to ethanol or control conditions during the neonatal period and transcript levels of bcl-2 family members relative to cyclophilin were determined. Pups exposed in parallel were taken for cerebellar cell counts. Results: Ethanol exposure during the first postnatal week significantly reduced Purkinje and granule cell numbers by postnatal day 21 (P21). Acute first postnatal week ethanol exposure up-regulated mRNA transcripts encoding the cell death-promoting molecules bax and bcl-xs as measured on P4. An additional day of exposure on P5 resulted in no further alterations in bcl-2 family transcripts, likely because Purkinje cell death was detectable as early as P5. To determine whether proapoptotic gene expression changes were specific to first postnatal week ethanol neurotoxicity, we examined bcl-2 family mRNA levels in rats exposed to ethanol during a developmental period of cerebellar insusceptibility, the second postnatal week. Exposure on P7 to P8 produced no change in cerebellar cell number, but also resulted in increased levels of bax, although only after 2-day ethanol exposure and not after acute exposure on P7. Conclusions: These data implicate altered expression of proapoptotic members of the bcl-2 gene family in acute ethanol-mediated cerebellar cell death during the first postnatal week. They also suggest that the differential survival of cerebellar neurons after ethanol exposure during more mature developmental stages may be related to more successful suppression of proapoptotic processes.