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Details

Autor(en) / Beteiligte
Titel
Regulation of α‐synuclein by bFGF in cultured ventral midbrain dopaminergic neurons
Ist Teil von
  • Journal of neurochemistry, 2003-02, Vol.84 (4), p.803-813
Ort / Verlag
Oxford, UK: Blackwell Science Ltd
Erscheinungsjahr
2003
Quelle
Wiley Online Library Journals【Remote access available】
Beschreibungen/Notizen
  • 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.

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