Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein

Merja Lakso, Suvi Vartiainen, Anu Maarit Moilanen, Jouni Sirviö, James H. Thomas, Richard Nass, Randy D. Blakely, Garry Wong

Research output: Contribution to journalArticle

247 Scopus citations

Abstract

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 alanine53 → threonine (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.

Original languageEnglish (US)
Pages (from-to)165-172
Number of pages8
JournalJournal of Neurochemistry
Volume86
Issue number1
DOIs
StatePublished - Jul 1 2003

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Keywords

  • Model organism
  • Motor neuron
  • Neurodegeneration
  • Worm transgenic
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Lakso, M., Vartiainen, S., Moilanen, A. M., Sirviö, J., Thomas, J. H., Nass, R., Blakely, R. D., & Wong, G. (2003). Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human α-synuclein. Journal of Neurochemistry, 86(1), 165-172. https://doi.org/10.1046/j.1471-4159.2003.01809.x