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Creation Date
4-19-2016
Description
Autophagy is a degradative process that enables cells to survive stress from nutrient deprivation, accumulation of damaged organelles, and pathogen invasion. In healthy cells, autophagy removes damaged proteins and organelles to prevent cell damage. In starving cells, autophagy digests intracellular molecules to provide the valuable nutrients cells need. Furthermore, dysfunctional autophagy, on the other hand, is implicated in aging, and many diseases such as cancer, neurodegenerative diseases, muscular disorders, diabetes, and obesity. Thus, understanding the underpinnings of autophagy in health and disease is an active area of today's research. Herein, we present our findings on the role of autophagy in the nervous system of Caenorhabditis elegans nematodes. To study the role of autophagy in neurons, we manipulated autophagy by reducing the levels of BEC-1, a protein shown to induce autophagy in eukaryotes from yeast to humans. In brief, BEC-1 expression in GABAergic motor neurons was blocked posttranscriptionally using tissue specific dsRNA knockdown strategies. Synchronous nematodes strain XE1375 were fed with bacteria containing an empty vector (control) or a vector possessing sequences for the expression of the bec-1 dsRNA (experimental). During development, GABAergic motor neurons of nematodes from strain XE 1375 were exposed to the inhibitory effects of the bec-1 dsRNA and results were recorded at various stages. Analyses of animals fed with bacteria expressing the bec- 1dsRNA show postembryonic developmental and functional defects at the level of motor neurons. Imaging studies with epifluorescent microscopy revealed a reduction in the number of VD motor neurons with an average count of 17 of the original 19 motor neurons. Quantification of motor function showed a statistically significant decrease in motility with control groups averaging 51 body bends per minute (bb/m) and the experimental group averaging 46 bb/m. Analysis of effects of enhanced autophagy by Rapamycin are currently underway and results will be presented at the meeting.