Welcome to the 2021 Senior Legacy Symposium!
Parkinson’s disease affects millions of people worldwide. Rotenone, a pesticide known to inhibit mitochondrial complex I, induces oxidative stress and α-synuclein aggregation leading to cell death of dopaminergic neurons in models of Parkinson's disease. Recent studies further implicate that rotenone may induce protein aggregation by impairing autophagy. Autophagy is a major cellular mechanism by which cells degrade damaged or unnecessary proteins and internal organelles for maintaining cellular energy balance. While mechanisms of rotenone’s toxicity in neurons are well determined, it is not known if rotenone triggers similar toxic pathways (i.e. autophagy deficit) in non-neuronal cells. Also, if there is protective agent that can help mitigate rotenone’s toxicity in cells.
We tested rotenone’s toxicity in an in vitro model of Lymnaea stagnalis’s hemocytes (blood cells). We also tested a neuroprotective drug, mitochondrial division inhibitor-I (Mdivi-1) to see if it could prevent rotenone toxicity. We hypothesized that rotenone would cause toxic effects and impact the autophagy signaling and that Mdivi-1 would reduce the toxicity of rotenone in Lymnaea hemocytes. To test our hypotheses, we cultured hemocytes in different concentrations of rotenone alone or in combination with Mdivi-1. After 24h , cells were fixed and stained with DAPI to label nuclei, beta-tubulin to label the cytoskeleton, and LC-B3 to label autophagy. The results demonstrate a dose-dependent toxicity of rotenone on cell survival and autophagy and that Mdivi-1 is able to protect cells from rotenone’s toxicity. These results expand our knowledge about rotenone toxicity in different cell types and help identify Mdivi-1 as a potential, protective agent. Acknowledgements: SLU College of Arts and Sciences Knoedler Research Award to Chidera Agwu and NSF IOS (1916563) to Dr. Fenglian Xu.
Chidera Agwu is from Denver, CO majoring in neuroscience and a minor in Health Care Ethics and Biology. Upon graduation he will be doing clinical neuroscience research before applying to medical school. He has been in Dr. Xu's research lab since 2019 working with snail neurons. His interests focus on neurodegenerative diseases and understanding their biological and physiological mechanisms.
Chidera would like to thank Dr. Fenglian Xu and Dr. Martina Rosato for all of their support in this project. Along with other members of the Xu lab.