Journal of Energy Bioscience 2025, Vol.16, No.1, 42-52 http://bioscipublisher.com/index.php/jeb 47 Figure 3Slc6a8xY389C/y KI males present reduced muscular mass and smaller myocytes (Adopted from Duran-Trio et al., 2021) Image caption: A, Urinary Crn (left panel) as well as plasmatic Crn and total CK levels (middle and right panel, respectively) as indicative of the muscular mass. Six WT and six KI: two-tailed t test. B, Significant decrease of Cr ([μmol/g tissue], two-tailed t test) and significant increase of GAA levels in muscle ([μmol/g tissue], Mann-Whitney test) in KI male rats, five WT and five KI. C, Representative macroscopic pictures of WT and KI male hind limbs in frontal/longitudinal (upper panels) and medial/inner lateral views (lower panels) showing reduced volume of quadriceps in KI male rats. D, Representative microscopic pictures of hematoxylin/eosin staining in transversal sections of WT and KI male quadriceps showing significant smaller myocyte diameter in KI males. Scale bar = 15 μm. E, Quantifications of myocyte minimum Feret diameter and cross-sectional area per each genotype. Mann-Whitney test, three WT, and three KI (319-382 measurements per WT and 414-555 per KI male). Statistical analysis was conducted with R-3.5.1. (R Core Team, 2018) Graphs were done using ggplot2 package. (Wickham, 2016) Cr, Creatine; Crn, creatinine; GAA, guanidinoacetate; KI, knock-in; WT, wild type. *P < .05; **P < .01; ***P < 0.001 (Adopted from Duran-Trio et al., 2021) 5.3 Implications in neurodegenerative diseases Creatine metabolism not only affects muscles, it is also important for the brain. Because the brain also requires a lot of energy, once the creatine system has problems, neurological function may also be impaired. If the creatine transporter is missing, it may cause intellectual problems, abnormal behavior, and even motor coordination disorders (Stockebrand et al., 2018; Duran-Trio et al., 2021). Some studies have also found that creatine may have a protective effect on nerves. It helps maintain cellular energy balance and reduces oxidative stress, potentially slowing the progression of neurodegenerative diseases (Balestrino and Adriano, 2019; Bonilla et al., 2021a). Currently, scientists are continuing to study the therapeutic effects of creatine supplementation on neuropathies. Research by Balestrino and Adriano (2019) showed that creatine supplementation may be helpful for diseases such as Huntington's disease and Parkinson's disease.
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