Over the past few decades several attempts have been made to introduce a potential and promising therapy for Multiple sclerosis (MS). Calorie restriction (CR) is a dietary manipulation to reduce calorie intake which has been shown to improve neuroprotection and attenuate neurodegenerative disorders. Here, we evaluated the effect of 33% CR regimen for 4 weeks on the remyelination capacity of Cuprizone (CPZ) induced demyelination in a mouse model of MS. Results showed that CR induced a significant increase in motor coordination and balance performance in CPZ mice. Also, luxol fast blue (LFB) staining showed that CR regimen significantly improved the remyelination in the corpus callosum of CPZ + CR mice compared to the CPZ group. In addition, CR regimen significantly increased the transcript expression levels of BDNF, Sox2, and Sirt1 in the corpus callosum of CPZ mice, while decreasing the p53 levels. Moreover, CR regimen significantly decreased the apoptosis rate. Furthermore, astrogliosis (GFAP + astrocytes) and microgliosis (Iba-1 + microglia) were significantly decreased by CR regimen while oligodendrogenesis (Olig2+) and Sirt1 + cell expression were significantly increased in the corpus callosum of CPZ + CR mice compared to the CPZ group. In conclusion, CR regimen can promote remyelination potential in a CPZ-demyelinating mouse model of MS by increasing oligodendrocyte generation while decreasing their apoptosis.

在过去的几十年里，人们进行了多次尝试来引入一种潜在且有前途的多发性硬化症（MS）疗法。热量限制（CR）是一种减少热量摄入的饮食控制，已被证明可以改善神经保护并减轻神经退行性疾病。在这里，我们评估了 33% CR 方案 4 周对铜宗 (CPZ) 诱导的 MS 小鼠模型脱髓鞘能力的影响。结果表明，CR 显着提高了 CPZ 小鼠的运动协调性和平衡能力。此外，勒克索尔坚蓝（LFB）染色显示，与CPZ组相比，CR方案显着改善了CPZ+CR小鼠胼胝体的髓鞘再生。此外，CR方案显着增加了CPZ小鼠胼胝体中BDNF、Sox2和Sirt1的转录表达水平，同时降低了p53水平。此外，CR方案显着降低了细胞凋亡率。此外，与 CPZ 组相比，CR 方案显着减少了 CPZ + CR 小鼠胼胝体中的星形胶质细胞增生（GFAP + 星形胶质细胞）和小胶质细胞增生（Iba-1 + 小胶质细胞），而少突胶质细胞生成（Olig2+）和 Sirt1 + 细胞表达显着增加。总之，CR 方案可以通过增加少突胶质细胞的生成同时减少其凋亡来促进 CPZ 脱髓鞘小鼠模型的髓鞘再生潜力。