Regulation of α-synuclein by bFGF in cultured ventral midbrain dopaminergic neurons

α-Synuclein is a neuronal protein that is implicated in the control of synaptic vesicle function and in Parkinson's disease (PD). Consequently, alterations of α-synuclein levels may play a role in neurotransmission and in PD pathogenesis. However, the factors that regulate α-synuclein levels are unknown. Growth factors mediate neurotrophic and plasticity effects in CNS neurons, and may play a role in disease states. Here we examine the regulation of α-synuclein levels in primary CNS neurons, with particular emphasis on dopaminergic neurons. E18 rat cortical neurons and dopaminergic neurons of E14 rat ventral midbrain showed an induction of α-synuclein protein levels with maturation in culture. Application of basic Fibroblast growth factor (bFGF) promoted α-synuclein expression selectively within dopaminergic, and not GABAergic or cortical neurons. This induction was blocked by actinomycin D, but not by inhibition of bFGF-induced glial proliferation. α-Synuclein levels were not altered by glial-derived neurotrophic factor (GDNF), or by apoptotic stimuli. We conclude that bFGF promotes α-synuclein expression in cultured ventral midbrain dopaminergic neurons through a direct transcriptional effect. These results suggest that distinct growth factors may thus mediate plasticity responses or influence disease states in ventral midbrain dopaminergic neurons.