Ethanol-induced alterations in neurotrophin expression in developing cerebellum: Relationship to periods of temporal susceptibility

Background: The developing cerebellum has been shown to be profoundly affec ted by exposure to ethanol and to exhibit a temporal pattern of vulnerabili ty. Cerebellar Purkinje cells are particularly susceptible to ethanol on po stnatal day 4 or day 5 (P4-5), whereas this population is much less vulnera ble to similar ethanol insult slightly later in the postnatal period (P7-9) . The purpose of the study was to determine whether differential alteration s in neurotrophic factors might be associated with this differential suscep tibility. Methods: Neonatal rats were exposed to ethanol via vapor inhalation, and en zyme-linked immunoabsorbent assays were subsequently conducted to assess ce rebellar nerve growth factor, brain-derived neurotrophic factor. and neurot rophin-3 protein content. These analyses were made after ethanol exposure d uring the period of maximal cerebellar ethanol sensitivity (postnatal days 4-5 [P4-5]), during a period of much lower sensitivity (P7-8), and during t he entire "brain growth spurt" (P4-10). Results: These determinations revealed a significant ethanol-induced decrea se in cerebellar nerve growth factor after exposure on P4-5 but not after e xposure on P7-8 or P4-10. No significant changes in brain-derived neurotrop hic factor or neurotrophin-3 were found with any of the exposure paradigms. Conclusions: These results suggest that alterations in nerve growth factor, which has previously been shown to support cerebellar Purkinje and granule cells, may be a mechanism contributing to the early ethanol susceptibility within these neuronal populations.