The Caenorhabditis elegans dopaminergic system: opportunities for insights into dopamine transport and neurodegeneration.
The neurotransmitter dopamine (DA) plays a central role in the coordination of movement, attention, and the recognition of reward. Loss of DA from the basal ganglia, as a consequence of degeneration of neurons in the substantia nigra, triggers postural instability and Parkinson's disease (PD). DA transporters (DATs) regulate synaptic DA availability and provide a conduit for the uptake of DA mimetic neurotoxins, which can be used to evoke neuronal death and Parkinson-like syndrome. Recently, we have explored the sensitivity of DA neurons in the nematode Caenorhabditis elegans to the Parkinsonian-inducing neurotoxin 6-hydroxydopamine (6-OHDA) and found striking similarities, including DAT dependence, to neurodegeneration observed in mammalian models. In this review, we present our findings in the context of molecular and behavioral dimensions of DA signaling in C. elegans with an eye toward opportunities for uncovering DAT mutants, DAT regulators, and components of toxin-mediated cell death.
Nass
Richard
R
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6420, USA. richard.nass@vanderbilt.edu
Blakely
Randy D
RD
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D017173:Caenorhabditis elegans / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D023421:Models, Animal; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism; D015398:Signal Transduction
D016627:Oxidopamine; D004298:Dopamine