Neuromuscular Synapse Dynamics in Aged and Injured Skeletal Muscle
Abstract
It is evident that both aged and diseased skeletal muscle exhibit interesting neuromuscular dynamics, characterized by changes in morphology and functionality of the synapse. Although they display a high regenerative capacity, skeletal muscles are still susceptible to nervous system perturbations and impacts of aging. Aged neuromuscular junctions (NMJs) demonstrate a diseased phenotype following some form of muscle atrophy, indicating the presence of paracrine signaling between myofibers and neuronal cells. In this study, we investigated differences in neuromuscular dynamics in injured and aged skeletal muscle using whole‐mount immunostaining and imaging. It has previously been shown that disruption of one component of the muscle microenvironment, such as vasculature, disrupts the structure of NMJs, however it is unclear if aged skeletal muscle experiences similar changes. We hypothesized that both aged and injured NMJs would display similar morphological dynamics, characterized by denervation and fragmentation of postsynaptic acetylcholine receptors (AChRs). We demonstrated that aged and injured NMJs exhibit fragmentation of AChRs, Wallerian degeneration of the presynaptic motor neurons, decreased overlap of pre‐ and post‐synaptic sides, and decreased area of AChR clusters. Due to the prevalence of neuromuscular disorders in the aging population, it is pertinent to understand nerve‐muscle interactions in the healthy aging state in order to hypothesize how these dynamics may be altered in the age‐induced injury states. Ultimately, this will allow us to better comprehend the molecular and cellular mechanisms that are responsible for neuromuscular degeneration in order to develop strategies to improve mobility and quality of life.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 01, 2022
- Source ID
- 10.1096/fasebj.2022.36.s1.r3239
Entities
People
- Berna Aliya
- Cade Jones
- Gunjae Jeong
- Hannah Castels
- Innie Kang
- Jeongmoon Choi
- Mahir Mohiuddin
- Young Jang
Organizations
- Georgia Tech
- National Institutes of Health
- United States Department of Defense