Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation

Neonatal rat cerebellar granule cells were used to assess the possible role of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway in the neur oprotective effects of neurotrophic factors against ethanol toxicity. Cultu re conditions included medium with ethanol (400 and 600 mg/dl), nerve growt h factor (NGF) or brain-derived neurotrophic factor (BDNF), ethanol + NGF o r BDNF, the PI3-K inhibitor wortmannin (10 or 100 mu M), and wortmannin + e thanol + NGF or BDNF. Neuronal survival was determined via the MTT assay. T he results indicated that both NGF and BDNF ameliorate ethanol neurotoxicit y, and wortmannin abolished this effect, except at the higher ethanol conce ntration combined with the lower wortmannin level. These data strongly impl icate the PI3-K pathway in growth factor protection against ethanol neuroto xicity. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.