Effects of electroacupuncture on motor function and PGC-1α/FNDC5/BDNF pathway in muscle and brain of SAMP8 mice

To observe the effect of electroacupuncture (EA) on motor function and skeletal muscle morphology in SAMP8 mice, and to explore the mechanisms of EA improving motor dysfunction in Alzheimer’s disease from the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/fibronectin type Ⅲ domain-containing protein 5 (FNDC5)/brain-derived neurotrophic factor (BDNF) pathway.

SAMP8 mice were randomly divided into model and EA groups, with 9 mice in each group. Nine anti-aging SAMR1 mice were used as control group. In the EA group, “Baihui”(GV20), “Dazhui”(GV14) and “Shenshu”(BL23) were needled with EA for 20 min every day, 8 d as a course of treatment, with an interval of 2 d between courses. A total of 3 courses was proceeded. The motor function of mice was detected by grasping test, swimming test, suspension test and hind limb clamping test. The morphological structure of gastrocnemius muscle was observed by HE staining. The positive expressions of PGC-1α, FNDC5 and BDNF in gastrocnemius muscle were observed by immunohistochemical staining. The expression levels of PGC-1α, FNDC5 and BDNF mRNAs in gastrocnemius muscle and cerebral motor cortex were detected by real-time fluorescence quantitative PCR. The expression levels of PGC-1α, FNDC5 and BDNF proteins in gastrocnemius muscle and cerebral motor cortex were detected by Western blot.

Compared with the control group, the peak grip strength, average and maximum swimming speed, and suspension test score of the model group were significantly decreased (P<0.01), and the hind limb clamping test score was significantly increased (P<0.01). The gastrocnemius muscle fibers were loose and irregularly arranged, the spacing was widened and the cytoplasmic staining was uneven. The positive expression area ratios of PGC-1α, FNDC5 and BDNF in gastrocnemius muscle were significantly decreased (P<0.01), and the relative expression levels of PGC-1α, FNDC5 and BDNF mRNAs and proteins in gastrocnemius muscle and cerebral motor cortex were significantly decreased (P<0.01). Compared with the model group, the peak grip strength, average and maximum swimming speed, and suspension test score of the EA group were significantly increased (P<0.01), and the hind limb clamping test score was significantly decreased (P<0.01). The muscle fibers were intact and arranged regularly, the spacing was narrowed, and the cytoplasmic staining was uniform.The positive expression area ratios of PGC-1α, FNDC5 and BDNF were significantly increased (P<0.01), and the relative expression levels of PGC-1α, FNDC5 and BDNF mRNAs and proteins in gastrocnemius muscle and cerebral motor cortex were significantly increased (P<0.01, P<0.05). The correlation analysis results of PGC-1α, FNDC5 and BDNF mRNA expression in gastrocnemius and cerebral motor cortex showed a highly positive correlation (r>0.70, P<0.01).

EA can improve motor dysfunction and skeletal muscle morphology in SAMP8 mice, and its mechanism may be related to up-regulation of PGC-1α, FNDC5 and BDNF expressions in gastrocnemius and cerebral motor cortex.