Suppression of Defective Motor Patterns in Parkinsonian C. elegans
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Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is caused partly by the loss of dopamine producing neurons. Dopamine is a conserved neuromodulator that aids in the transition between different motor patterns such as swimming, walking, or running. This can be observed across many species, including mice, flies, and nematodes. The cat-2 mutant strain of the nematode C. elegans has a deletion in the gene encoding tyrosine hydroxylase, an enzyme required to synthesize dopamine. Our lab recently demonstrated that the cat-2 mutant shares aspects of PD patient dysfunction through its inability to transition normally between the “swimming” and “crawling” patterns of motion. Currently, PD treatments focus on boosting residual dopamine signaling and are not available to maintain motor function once dopamine neurons completely degenerate. To search for ways to overcome motor dysfunction in the absence of dopamine, we performed a forward genetic screen to identify mutations that suppress poor swim-to-crawl motor transition in cat-2 mutant. We found several suppressor mutants that improve motor function. Further characterization can identify molecular pathways that can be altered to improve motor function in the absence of dopamine. This information could provide insight into repair of dopamine-deficient neural circuitry in higher level animals and possible approaches to help late stage PD patients.