Examining the Effects of Environmental Toxins on Amyotrophic Lateral Sclerosis (2023)

Undergraduate: Vanya Bhat

Faculty Advisor: Todd Cohen
Department: Neurology, Psychology & Neuroscience

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ALS is a progressive neurodegenerative disease that affects neurons that control voluntary muscle movements. Environmental toxins such as pesticides and fungicides have been found to be potential causal factors for ALS as they may lead to the formation of toxic TDP-43 aggregation, a hallmark of the disease. Reactive oxygen species (ROS) lead to the formation of these toxic aggregates causing cell death. This study examined whether four pesticides: TS1, TS3, TS21, and TS31, induce toxic TDP-43 aggregation and whether oxidative stress is involved in response to the pesticides. Two experiments were conducted with primary cortical neurons that were isolated from wildtype mice embryos. Neurons were co-exposed to a sublethal dose exposure of the pesticides and reactive oxygen species inhibitors (cotreatments). Results showed that TS1 and TS3 caused TDP-43 toxic aggregation. Additionally, cotreatments that chelated zinc and copper had various degrees of recovery depending on the drug and cotreatment dosage. TS21 and TS31 did not cause toxic TDP-43 aggregation unless cotreated with ZnCl, which increased the intracellular levels of zinc. Further studies must be done with these toxins to determine how they lead to ALS pathology.

Key Words: ALS, TDP-43 aggregation, reactive oxygen species, zinc, pesticides

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