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.