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 affected by exposure to ethanol and to exhibit a temporal pattern of vulnerability. Cerebellar Purkinje cells are particularly susceptible to ethanol on postnatal day 4 or day 5 (P4-5), whereas this population is much less vulnerable to similar ethanol insult slightly later in the postnatal period (P7-9). The purpose of the study was to determine whether differential alterations in neurotrophic factors might be associated with this differential susceptibility. METHODS: Neonatal rats were exposed to ethanol via vapor inhalation, and enzyme-linked immunoabsorbent assays were subsequently conducted to assess cerebellar nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 protein content. These analyses were made after ethanol exposure during the period of maximal cerebellar ethanol sensitivity (postnatal days 4-5 [P4-51), during a period of much lower sensitivity (P7-8), and during the entire "brain growth spurt" (P4-10). RESULTS: These determinations revealed a significant ethanol-induced decrease in cerebellar nerve growth factor after exposure on P4-5 but not after exposure on P7-8 or P4-10. No significant changes in brain-derived neurotrophic 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 neuronar populations.