Ethanol induced changes in cyclin-dependent kinase-5 activity and its activators, P35, P67 (Munc-18) in rat brain.

The expression of cyclin-dependent kinase-5 (Cdk5) and its regulators, p35 and p67 was investigated in adult rat cerebral cortex and cerebellum, using an experimental paradigm of in vivo chronic ethanol exposure. In parallel, the activity of Cdk5 kinase was measured using a specific substrate histone-H1 peptide. Western blot analysis revealed no appreciable change in the expression of Cdk5 protein levels while, its regulatory proteins, p35 and p67 showed decreased levels following chronic ethanol treatment. However, ethanol treatment resulted in increased Cdk5 activity in both cortex and cerebellum with relatively high activity in cortex. Given the abundant expression and functions of Cdk5 in neural cells, our data implies a regulatory role for Cdk5 in ethanol mediated cell injury and may contribute to impaired CNS development in brain atrophy associated with alcoholic neurodegeneration.