Regulation of alpha-synuclein by bFGF in cultured ventral midbrain dopaminergic neurons.
Alpha-synuclein is a neuronal protein that is implicated in the control of synaptic vesicle function and in Parkinson's disease (PD). Consequently, alterations of alpha-synuclein levels may play a role in neurotransmission and in PD pathogenesis. However, the factors that regulate alpha-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 alpha-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 alpha-synuclein protein levels with maturation in culture. Application of basic Fibroblast growth factor (bFGF) promoted alpha-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. alpha-Synuclein levels were not altered by glial-derived neurotrophic factor (GDNF), or by apoptotic stimuli. We conclude that bFGF promotes alpha-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.
Rideout
Hardy J
HJ
Department of Neurology, Columbia University, Black Building Room 326, 650 W. 168th Street, New York, NY 10032, USA. hr227@columbia.edu
Dietrich
Paula
P
Savalle
Magali
M
Dauer
William T
WT
Stefanis
Leonidas
L
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051843:Synucleins; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D051844:alpha-Synuclein; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C497605:Snca protein, mouse; C497606:Snca protein, rat; D051843:Synucleins; D051844:alpha-Synuclein; D016222:Fibroblast Growth Factor 2; D005680:gamma-Aminobutyric Acid; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine