Ischemia induces changes in SOD activity and neuromuscular regeneration

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Aliya, Berna
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Critical limb ischemia (CLI) is characterized as a neuromuscular disorder of aging that develops due to an occlusion of blood flow to the affected lower limbs. Following ischemic injury, disruption of vasculature interrupts delivery of oxygen and nutrients to motor neurons and subsequently results in degeneration of the neuromuscular junctions (NMJs). This induces further myofiber atrophy due to the lack of innervation from the presynaptic motor neurons to the myofibers. Recent regenerative medicine approaches have investigated the role of redox homeostasis in the regeneration of ischemic skeletal muscle. Superoxide dismutases (SOD1 and SOD2) are key enzymes that regulate reactive oxygen species and help to maintain redox homeostasis and the regenerative capacity of myofibers. Research investigating the redox signaling in the crosstalk between ischemic myofibers and motor neurons has been limited. Our research question is: how does redox signaling impact neuromuscular regeneration following injury? We hypothesize that dysregulated SOD enzymes correlates to altered morphology of the neuromuscular junctions following ischemia. To test our hypothesis, we induced ischemia in a mouse model and performed microscopic imaging and biochemical assays in muscle and nerve cells in various time points following ischemic injury. Our results indicate that ischemic injury results in denervation of the motor neuron and fragmentation of postsynaptic acetylcholine receptors (AChR). We also concluded that there is a disruption in the SOD enzymes in the muscle microenvironment upon injury that corresponds with the morphological changes in the NMJs that were witnessed. By understanding this correlation between the innervation and fragmentation of NMJs and the SOD specific activity, the essential role of redox homeostasis in maintaining and regenerating a functional neuromuscular system can be better understood.
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Undergraduate Thesis
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