Cecilia He
Pronouns: she/her
Research Mentor(s): Steve Guzman
Research Mentor School/College/Department: Molecular and Integrative Physiology / Medicine
Program: UROPF
Session: Session 6 (3:40pm – 4:30pm)
Authors: Cecilia He, Steve Guzman
Abstract
The neuromuscular junction (NMJ) is the primary site of communication between the central nervous system and skeletal muscles. Degenerative changes in the NMJ would subsequently lead to deficits in skeletal muscle function. The cellular components of the NMJ include the motor neuron, muscle fiber, and perisynaptic Schwann Cells (SC). Our group has previously shown that mice lacking the critical antioxidant enzyme, Sod1, show extensive NMJ structure abnormalities, loss of skeletal muscle mass, and reduced force generation as early as 6 months of age. However, it is unclear how oxidative stress or lack of Sod1 at the onset of the disease affects perisynaptic Schwann cell function. Previous studies have shown that upon nerve injury in normal mice, there is a 2-3 fold increase in Schwann cell number in the nerve between ~2-10 weeks after injury, which is important for normal muscle reinnervation. Given that Sod1-/- mice show increased denervation, we wanted to determine the number of muscle-resident Schwann cells at the onset of the disease. We hypothesize that Sod1-/- mice at 2 months of age will show an increased number of muscle-resident Schwann cells accompanied by a decrease in muscle fiber number and cross-sectional area (CSA). We will test this by performing immunofluorescent imaging of gastrocnemius and tibialis anterior muscles in cross-section and determine the number of peri- and extra-synaptic Schwann cells as well as the number of muscle fibers and their cross-sectional area (CSA). We anticipate at least a two-fold increase in both peri- and extra-synaptic Schwann cells and a decrease in the cross-sectional areas of the muscle fibers in Sod1-/- mice compared to wild-type controls. These findings would suggest that muscle-resident Schwann cells react to oxidative stress-induced denervation by proliferating near the NMJ. Understanding the regenerative response to both oxidative stress and denervation by Schwann cells will help us better understand the critical physiological processes that have the potential to enhance regeneration in neuromuscular degenerative diseases such as sarcopenia and amyotrophic lateral sclerosis.
