[
International Worm Meeting,
2021]
Neurodegenerative diseases predominantly affect older cohorts, but the first misfolding processes occur earlier in life, prior to diagnosis. Therefore, the ability to monitor health prior to the onset of severe symptoms will be informative in the search for preventative interventions and in understanding disease onset. There are several C. elegans models of neurodegeneration but manual assays are subjective, labour intensive and provide binary data at single time points per animal - namely time of paralysis. An automated imaging system to monitor worm movement can assist by simultaneously revealing in-depth movement data unavailable to manual methods and scaling to study hundreds of plates of animals more easily. We have developed a technology that monitors plates of 6 cm petri dishes, with 30 worms on each. Using strains expressing polyglutamine tracts and amyloid-beta, we show that the presence of these transgenes is associated with early-life movement decline. Furthermore, there are differences in decline pattern dependent on whether the polyQ tract is expressed in body wall muscle or pan-neuronally, and on what treatments are used to prevent progeny such as FUdR or temperature sensitive sterile backgrounds. These findings allow the development of a robust system on which to screen mutants and pharmaceutical therapies. Our particular interest is drugs that influence E. coli as a model for microbiome interventions. We have found that inhibiting bacterial folate synthesis using sulfamethoxazole (SMX) extends C. elegans lifespan and healthspan, and here we also show the effect of SMX on various neurodegenerative models. This approach therefore becomes a model of gut microbiome-host interaction which can streamline the selection of therapies for further testing on mammal models in the drug discovery pipeline.