Present address: Departments of Anesthesiology and Pharmacology, and Center for Molecular Neuroscience, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein
Article first published online: 4 FEB 2004
Journal of Neurochemistry
Volume 86, Issue 1, pages 165–172, July 2003
How to Cite
Lakso, M., Vartiainen, S., Moilanen, A.-M., Sirviö, J., Thomas, J. H., Nass, R., Blakely, R. D. and Wong, G. (2003), Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein. Journal of Neurochemistry, 86: 165–172. doi: 10.1046/j.1471-4159.2003.01809.x
- Issue published online: 4 FEB 2004
- Article first published online: 4 FEB 2004
- Received January 23, 2003; revised manuscript received March 19, 2003; accepted March 19, 2003.
- model organism;
- motor neuron;
- worm transgenic
Overexpression of human α-synuclein in model systems, including cultured neurons, drosophila and mice, leads to biochemical and pathological changes that mimic synucleopathies including Parkinson's disease. We have overexpressed both wild-type (WT) and mutant alanine53threonine (A53T) human α-synuclein by transgenic injection into Caenorhabditis elegans. Motor deficits were observed when either WT or A53T α-synuclein was overexpressed with a pan-neuronal or motor neuron promoter. Neuronal and dendritic loss were accelerated in all three sets of C. elegans dopaminergic neurons when human α-synuclein was overexpressed under the 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 between worms of different ages (4 days, 10 days or 2 weeks). These results demonstrate neuronal and behavioral perturbations elicited by human α-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 help facilitate dissection of pathophysiologic mechanisms of various synucleopathies.