[
International Worm Meeting,
2003]
Overexpression of human - synuclein in model systems, including cultured neurons, drosophila, and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinsons disease (PD). We have overexpressed both wild-type (WT) and mutant alanine53 threonine (A53T) human -synuclein by transgenic injection to Caenorhabditis elegans. Motor deficits were observed when either WT or A53T -synuclein were overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all 3 sets of C. elegans dopaminergic neurons when human -synuclein was overexpressed under control of a dopaminergic neuron or pan-neuronal promoter, but not with a motor neuron promoter. There were no significant differences in neuronal loss between overexpressed WT and A53T forms or whether the worms were scored at 4 d, 10 d, or 2 weeks. These results demonstrate neuronal and behavioral perturbations elicited by human -synuclein in C. elegans that are dependent upon expression in specific neuron subtypes. This transgenic model in C. elegans, an invertebrate organism with excellent experimental resources for further genetic manipulation, may provide insights to facilitate dissection of pathophysiologic mechanisms of various synucleopathies.