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Miller Lab

Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans

AUTHORS

Nass RRichard , Hall DHDavid H , Miller DMDavid M , Blakely RDRandy D . Proceedings of the National Academy of Sciences of the United States of America. 2002 02 26; 99(5). 3264-9

ABSTRACT

Parkinson’s disease is a complex neurodegenerative disorder characterized by the death of brain dopamine neurons. In mammals, dopamine neuronal degeneration can be triggered through exposure to neurotoxins accumulated by the presynaptic dopamine transporter (DAT), including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium. We have established a system for the pharmacological and genetic evaluation of neurotoxin-induced dopamine neuronal death in Caenorhabditis elegans. Brief (1 h) exposure of green fluorescent protein-tagged, living worms to 6-OHDA causes selective degeneration of dopamine neurons. We demonstrate that agents that interfere with DAT function protect against 6-OHDA toxicity. 6-OHDA-triggered neural degeneration does not require the CED-3/CED-4 cell death pathway, but is abolished by the genetic disruption of the C. elegans DAT.