Abstract

Sporadic amyotrophic lateral sclerosis (SALS) is a fatal neurodegenerative disease affecting the human motor system that clinically presents itself as muscle weakness which becomes widespread over time leading to death. The cause of SALS is unknown. A non-protein amino acid, beta-N-methylamino-L-alanine (BMAA), has been found to bioaccumulate in the brain after ingestion causing the release of reactive oxygen species (ROS), which leads to neurodegeneration, creating SALS symptoms. Vitamin E has been shown to clear ROS out of neuronal cells. The hypothesis being tested is if vitamin E is able to remove some of the ROS that is released in the brain due to BMAA toxicity, then it will decrease the amount of neurodegeneration caused by the ROS. The specific aims of this research are (1) to see whether vitamin E has dose-dependent effects on the amount of ROS in motor neurons, (2) to determine if vitamin E can prevent some of the neuronal damage caused by ROS release when consumed a significant amount of time before ingestion of BMAA, and (3) to see whether the induction of excitotoxicity increases or decreases the amount of ROS that vitamin E removes. Cynomolgus macaque monkeys will be used in the experiments for each aim. The level of neurodegeneration in the monkeys will be determined weekly by measuring limb function using electrical scalp stimulation. Vacuolation, a sign of impending neuron death, will be measured in the monkeys’ motor neurons after 20 weeks once the monkeys have been euthanized. The expected results are that vitamin E will be most effective at removing ROS (1) at the highest dose used, (2) when it starts being administered a significant amount of time before ingestion of BMAA, and (3) when excitotoxicity is induced. These results will provide more information about whether vitamin E can be used to prevent the neurotoxic effects of BMAA ingestion and how vitamin E can be used most effectively to clear away ROS.