Survival factors promote BDNF protein expression in mesencephalic dopaminergic neurons

The aim of the present study was to characterize signals and/or molecules which regulate BDNF protein expression in mesencephalic dopaminergic neurons. Treatment of mesencephalic cells with dibutyryl-cAMP (dbcAMP), 30 mM K (HK), or the antimitotic ara-C not only promoted the survival of tyrosine hydroxylase expressing (TH) neurons but also increased the proportion of these cells that were immunopositive for BDNF. The effect of dbcAMP was mimicked by forskolin, a known adenylate cyclase activator. It was not antagonized by PKA inhibitors. Increases in BDNF expression resulting from K-induced depolarization or ara-C treatment were abolished, respectively, by the L-type calcium channel blocker nifedipine and the deoxynucleotide dCTP. BDNF added exogenously to the cultures improved the survival of TH neurons. However, induction of the expression of BDNF in these neurons by dbcAMP, HK or ara-C was apparently not responsible for survival promotion by these factors.