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Regulation of α‐synuclein by bFGF in cultured ventral midbrain dopaminergic neurons
Author(s) -
Rideout Hardy J.,
Dietrich Paula,
Savalle Magali,
Dauer William T.,
Stefanis Leonidas
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01574.x
Subject(s) - dopaminergic , glial cell line derived neurotrophic factor , neuroscience , midbrain , neurotrophic factors , biology , neurotrophin , gdnf family of ligands , basic fibroblast growth factor , oxidopamine , dopamine , substantia nigra , central nervous system , growth factor , biochemistry , receptor
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.