Ethanol exposure during development leads to alterations in neuronal differentiation and profound neuronal loss in multiple regions of the developing brain. Although differentiating Purkinje cells of the cerebellum are particularly vulnerable to ethanol exposure, the mechanisms that ameliorate ethanol-induced Purkinje cell loss have not been well defined. Previous research indicates that glial-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta family, promotes the survival of several neuronal populations, including cerebellar Purkinje cells. Therefore, we examined whether GDNF could attenuate ethanol-induced Purkinje cell loss in an in vitro model system using calbindin-D28k immunoreactivity as a specific marker for Purkinje cells. We found that ethanol led to a significant dose-related decline in calbindin-D28k-immunoreactive cells in explant cultures of the developing cerebellum. However, concurrent administration of GDNF led to a significant rescue of calbindin-D28k-immunoreactive cells. Therefore, our results suggest that GDNF prevents ethanol-associated Purkinje cell loss.
