Research Paper Volume 15, Issue 5 pp 1306—1329

AAV1.NT-3 gene therapy prevents age-related sarcopenia

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Figure 4. NT-3 gene transfer improves myelin thickness of peripheral nerves and neuromuscular junction assembly in C57BL/6 mice. Representative semithin, toluidine blue–stained cross-sections of tibial nerves from (A) treated and (B) untreated C57BL/6 mice. Scale bar = 10 μm. (C) Myelin thickness significantly decreased with age in 2-year-old mice compared to 1-year-old counterparts (1 yo, r2 = 0.0363; 2 yo, r2 = 0.2245; Linear regression, slopes are significantly different, p < 0.0001). (D) The shift toward thinner myelin can also be observed in percent distribution graph with aging. (E) A notable increase of myelin thickness was observed with treatment compared to samples from untreated (NT-3, r2 = 0.0989; UT, r2 = 0.2245; Linear regression, slopes are significantly different, p = 0.0037) and (F) percent analysis of g ratio of treated cohort displayed a distribution that peaks at 0.6 (n = 6 for both treated and untreated 2-year-old mice, n = 4 for 1-year-old control mice, with even sex distribution). (G) Representative image showing innervated (I), partially innervated (PI) and denervated (D) NMJs from the lumbrical muscles of the aged C57BL/6 mice. Scale bar = 10 μm. (H) Percent of the innervated NMJs in the treated mice was significantly higher than the untreated mice (*p = 0.0123). We evaluated an average of 41.2 NMJs per mouse (n = 4 mice for each cohort with equal sex distribution). Data is represented as mean ± SEM; Two-way ANOVA, Sidak’s multiple comparisons test; *p < 0.05.