AAV1.NT‐3 gene therapy in the SOD1KO mouse model of accelerated sarcopenia

Autor: Lingying Tong, Burcak Ozes, Kyle Moss, Morgan Myers, Alicia Ridgley, Zarife Sahenk
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 14, Iss 5, Pp 2204-2215 (2023)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.13303
Popis: Abstract Background Sarcopenia, an age‐related loss of muscle mass, is a critical factor that affects the health of the older adults. The SOD1KO mouse is deficient of Cu/Zn superoxide dismutase, used as an accelerated aging model. We previously showed that NT‐3 improves muscle fibre size by activating the mTOR pathway, suggesting a potential for attenuating age‐related muscle loss. This study assessed the therapeutic efficacy of AAV1.NT‐3 in this accelerated aging model. Methods Twelve 6 months old SOD1KO mice were injected intramuscularly with a 1 × 1011 vg dose of AAV1.tMCK.NT‐3, and 13 age‐matched SOD1KO mice were used as controls. The treatment effect was evaluated using treadmill, rotarod and gait analyses as well as histological studies assessing changes in muscle fibre, and fibre type switch, in tibialis anterior, gastrocnemius, and triceps muscles, and myelin thickness by calculating G ratio in sciatic and tibial nerves. Molecular studies involved qPCR experiments to analyse the expression levels of mitochondrial and glycolysis markers and western blot experiments to assess the activity of mTORC1 pathway. Results Treatment resulted in a 36% (154.9 vs. 114.1; P
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