Sophie Chong
Pronouns: she/her
Research Mentor(s): Lloyd Ruiz
Research Mentor School/College/Department: Molecular & Integrative Physiology / Medicine
Program: UROPF
Session: Session 4 (1:40pm – 2:30pm)
Authors: Sophie Chong, Sophie Chong, Lloyd Ruiz, Peter MacPherson, Susan V. Brooks
Abstract
Introduction: Sarcopenia, age-related loss of muscle mass, is an increasing health concern among the aging population (Dao et al., 2020). However, the mechanism for neuromuscular (NMJ) degradation remains unknown. Recent studies suggest the number of synaptic nuclei decline with age (Ang et al., 2022, Bai et al., 2022) and deletion of Lamin A/C may be related to the phenomenon (Gao, 2020). However, further understanding of Lamin A/C at the NMJ is required. Methods: Wildtype C57BL/6 mice were randomly assigned to a sciatic nerve transection group which allowed 3 or 7 days to recover following injury. Mice were anesthetized and carprofen was administered as a preemptive analgesic. The hindlimbs were carefully shaved and the skin was cleaned. An incision (<10 mm) was made 1 mm posterior and parallel to the femur. The superficial biceps femoris was split to expose the sciatic nerve, which was then transected. Using wound clips, the incision was closed. Quantitative-polymerase chain reaction (qPCR), western blots, and immunohistochemistry (IHC) on the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles were performed. Results: LMNA expression is upregulated in the muscle 7 days after sciatic nerve transection (p<0.005) and remains elevated at 14 days post injury (p<0.005) when compared to uninjured controls. Additional targets that showed upregulation include YAP, TAZ1, and AChR-a. YAP was significantly elevated (p<0.0005) following a 7-day injury. TAZ1 and AChR - a were also elevated (p<0.0005) from control to a 14-day injury. Immunohistochemistry of the tibialis anterior supports increased Lamin A/C signal localized to the NMJ. Conclusion: These preliminary results suggest LMNA transcription is upregulated and Lamin A/C protein levels are increased in the muscle following nerve injury. The mechanosensitive YAP/TAZ also appears responsive to nerve injury. Further study aims to evaluate the role of Lamin A/C in nerve regeneration conditions.
