1,2Kholoud M. Al-Otaibi, 3,4Badrah S Alghamdi, 1Maryam A. Al-Ghamdi, 1Ulfat Omar
1Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Chemistry, Faculty of Science, Al-Baha University, Al-Baha, Saudi Arabia; 3Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
Multiple sclerosis (MS) is a chronic demyelination disease of the central nervous system (CNS) that attacks the myelin sheath around the axon and damages it. Therefore, promoting remyelination is a critical strategy for treating MS to resolve and alleviate symptoms and protect myelin sheath from further damage. Vitamin D3 (Vit D3) supplementation is increasingly advised to patients with MS. Thus, this study aimed to investigate the effects of Vit D3 supplementation to improve remyelination in a cuprizone (CPZ) mouse model of MS.
Material(s) and Method(s):
The study was designed as two stages (de and re-myelination) for nine weeks; a total of 45 male SWR/J mice were divided into two groups, Control (n=15) and CPZ (n=30) groups for the first five weeks (demyelination stage). Mice in the control group were received a normal diet with ad libitum access through all experiment stages (de and re-myelination), whereas mice in the CPZ group were fed a diet mixed with 0.3% CPZ for 5 weeks to induce demyelination. After week 5 CPZ diet was discontinued and followed by a normal diet for the last 4 weeks (remyelination stages), and mice in the CPZ group were re-divided into two groups: untreated and treated with Vit D3 orally once daily at 800 IU/kg. The effect of Vit D3 on behavioral changes was determined using grip strength meter and rotarod test. The degree of de and re-myelination in the corpus callosum (CC) of brains were assessed by Luxol Fast Blue (LFB) stain at weeks 5, 7, and 9.
The results showed that CPZ significantly reduced behavior performance in mice and myelin content in CC during the demyelination stage. In contrast, mice’s grip strength and motor coordination performance revealed significantly improved behavior after treatment with Vit D3 at early and last remyelination stages (7 and 9 weeks, respectively). Furthermore, LFB staining showed that Vit D3 significantly promoted remyelination in the CC of the brain compared to the untreated group at the remyelination stages.
In conclusion, these results demonstrated that Vit D3 could improve remyelination in a CPZ-demyelinating mouse model of MS.