Effects of creatine supplementation on muscle metabolism in an Alzheimer mouse model
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Alzheimer’s disease (AD), the most common form of dementia in the elderly, is a global issue affecting about 24 million individuals. Because AD is a systemic pathology, dementia is not the only leading factor contributing to loss of independence in AD patients. AD may also impair skeletal muscle metabolism and function. Creatine (CR) supplementation may enhance skeletal muscle hypertrophy/mass and function in sarcopenia and muscular dystrophies, but has yet to be studied in AD. This study examined the effect of oral CR on muscle metabolism in a triple-transgenic (3xTg) AD mouse model. Twenty-four, 3×Tg AD mice (~8 month-old) were randomly assigned to control (CON) or CR (3% w/w) diet. Bodyweights and feed intakes were measured throughout the 8-week study. Lower limb (quadriceps muscle; QM and gastrocnemius; GM) and upper limb muscles (triceps; TM) were collected to analyze levels of CR, total protein, DNA, RNA, amino acids (AA), adenosine triphosphate (ATP), adenosine diphosphate (ADP), total and phosphorylated p70 ribosomal S6 kinase (p70S6K). Data (mean ± SEM) were assessed by analysis of variance (ANOVA) and Fisher’s least significant difference (LSD) post hoc test. In comparison to the CON group, CR supplementation increased CR content in both GM (p=0.002) and QM (p=0.037), with higher (p=0.032) ATP/ADP ratio in CR in comparison with CON in QM. A higher protein concentration (p<0.0001) was notable in GM of CR supplemented group vs. CON. Total branched-chain AA levels in QM increased 2-fold (p< 0.0001) in CR groups. Additionally, CR resulted in a higher (p<0.05) protein/DNA ratio; an index of muscle cell size, in both QM and GM for CR groups. The index of cell capacity for protein synthesis (RNA/DNA ratio) in GM was also higher (p=0.001) in CR groups. However, phosphorylation (activation) level of p70S6K, an integral component in protein synthesis signalling pathway, did not show any significant differences in female (p=0.161) and male (p=0.292) CR supplemented groups compared with CON. To conclude, CR supplementation is capable of inducing muscle hypertrophy/growth parameters in the 3×Tg AD mouse model, thereby enhancing protein synthesis capacity in skeletal muscles, thus possibly promoting muscle function in AD.