Tyrosine kinase inhibitors and cycloheximide inhibit Li+ protection of cerebellar granule neurons switched to non-depolarizing medium.

Recently, it has been shown that Li+ robustly enhances the survival of cerebellar granule neurons acutely switched to non-depolarizing medium after maturing in vitro, a condition which elicits massive apoptotic death in this cell type. Tyrosine protein phosphorylation is known to underlie the activity of a number of trophic factors. This prompted us to investigate whether specific tyrosine kinase inhibitors could modulate the Li+ protection of cultured granule neurons switched to non-depolarizing medium. Genistein and herbimycin A dose dependently abolished the Li+ effect. Furthermore, this effect was substantially prevented by the translational inhibitor cycloheximide, suggesting that it requires de novo protein synthesis. Overall, these results suggest that Li+ protection of cerebellar granule neurons switched to non-depolarizing medium involves tyrosine kinases and transcriptional activation.