Stimulation of remyelination is critical for the treatment of multiple sclerosis (MS) to alleviate symptoms and protect the myelin sheath from further damage. The current study aimed to investigate the possible therapeutic effects of combining vitamin D3 (Vit D3) and siponimod (Sipo) on enhancing remyelination and modulating microglia phenotypes in the cuprizone (CPZ) demyelination mouse model. The study was divided into two stages; demyelination (first 5 weeks) and remyelination (last 4 weeks). In the first 5 weeks, 85 mice were randomly divided into two groups, control (n = 20, standard rodent chow) and CPZ (n = 65, 0.3% CPZ mixed with chow for 6 weeks, followed by 3 weeks of standard rodent chow). At week 5, the CPZ group was re-divided into four groups (n = 14) for remyelination stages; untreated CPZ (0.2 ml of CMC orally), CPZ+Vit D3 (800 IU/kg Vit D3 orally), CPZ+Sipo (1.5 mg/kg Sipo orally), and CPZ+Vit D3 (800 IU/kg Vit D3) + Sipo (1.5 mg/kg Sipo orally). Various behavioral tasks were performed to evaluate motor performance. Luxol Fast Blue (LFB) staining, the expression level of myelin basic protein (MBP), and M1/M2 microglia phenotype genes were assessed in the corpus callosum (CC). The results showed that the combination of Vit D3 and Sipo improved behavioral deficits, significantly promoted remyelination, and modulated expression levels of microglia phenotype genes in the CC at early and late remyelination stages. These results demonstrate for the first time that a combination of Vit D3 and Sipo can improve the remyelination process in the cuprizone (CPZ) mouse model by attenuating the M1 microglia phenotype. This may help to improve the treatment of MS patients.

Background: Mental health issues among medical students have gained increasing attention globally, with studies indicating a high prevalence of psychological disorders within this population. The use of antidepressants and anti-anxiety medications has become a common response to these mental health challenges. However, it is crucial to understand the extent of their usage and associated effects on students’ mental health and academic performance. This cross-sectional study explored the use of antidepressants and anti-anxiety drugs and their impact on the mental health of medical students in Saudi Arabia. Methods: A cross-sectional survey of 561 medical students from 34 universities was conducted between March and July 2024. An anonymous online questionnaire was used to collect sociodemographic, mental health, and medication usage-related information. Results: Most of the participants were female (71.5%) and aged 21–25 years (62.7%). Approximately 23.8% of them used antidepressants, 5.6% reported using anti-anxiety medications, and 14.0% used both types of medication. Among the medication users, 71.7% were using selective serotonin reuptake inhibitors (SSRIs), and 28.3% were using other medications. Adverse drug reactions were reported by 58.8% of the participants, and 39.6% changed drugs with inadequate efficacy. Notably, 49.0% of the respondents who have ever used medications discontinued their medication without consulting a healthcare professional. Despite these challenges, 62.0% of the participants felt that their medications had a positive impact on their academic performance, 73.4% believed that the benefits outweighed the drawbacks, and 76.2% expressed a willingness to continue taking their medication. In particular, 77.6% agreed that treatment with these drugs could prevent mental breakdowns. Sleep duration, physical activity, and family history of psychiatric disorders were significantly associated with medication use, with p values of 0.002, 0.014, and 0.042, respectively. Conclusions: These results shed light on the need to understand the prescribing practices of antidepressant and anti-anxiety drugs among medical students while promoting the appropriate use of these medications among the students. There is a need to incorporate mental health interventions into counseling services and awareness programs to support students. Future longitudinal studies are needed to explore long-term trends.

Background:The cuprizone (CPZ) model has been used to study de- and re-myelination in mice; Previous studies have used different routes for CPZ intoxication, but the results were highly variable.Methods:Here, we compared demyelination induced by the administration of 0.3% CPZ mixed with ground rodent chow and a 400 mg/kg CPZ suspension in carboxymethyl cellulose (CMC) via oral gavage in SWR/J mice. The mice were assigned into a control group, a CPZ diet group, and an oral CPZ groups (n = 6 mice/group). Rotarod, hanging wire, and open field tests were performed to evaluate locomotor activity. Histological analyses were conducted on the corpus callosum (CC) of the brain to determine myelin loss and on the liver to assess the toxicity of CPZ.Results:The administration of CPZ with ground rodent chow significantly reduced body weight gains, grip strength, and motor coordination performance during the 5-week demyelination period. In contrast, all analyzed parameters were less different in mice receiving CPZ via oral gavage. However, both CPZ routes significantly reduced myelin content in the CC. Additionally, the oral administration of CPZ had strong effects on liver toxicity compared to that of CPZ diet feeding. This study showed that both routes of CPZ intoxication could induce reproducible and consistent demyelination changes within the CC of the mouse brain, with the CPZ diet being more effective based on all analytical parameters and having fewer toxic effects on the liver compared with oral CPZ.Conclusions:In conclusion, the resultsassist in the selection of a suitable multiple sclerosis (MS) model for investigating disease mechanisms and therapies.

Background/Objectives: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, and axonal loss. Despite available therapies, there is currently no effective cure for MS. Ibudilast (IBD), a phosphodiesterase inhibitor, and 6-shogaol (SH), a bioactive compound from ginger, have independently shown therapeutic potential in MS models. This study aimed to evaluate the therapeutic efficacy of combining SH and IBD in modulating neuroinflammation and improving functional recovery in a cuprizone (CPZ) mouse model of MS. Methods: Male SWR/J mice were exposed to 0.3% CPZ for 5 weeks to induce demyelination, followed by 4 weeks of spontaneous remyelination after CPZ withdrawal. During remyelination, the CPZ group was subdivided into four groups: no therapy, SH (25 mg/kg), IBD (10 mg/kg), and SH + IBD. Behavioral tests were used to assess locomotion, muscle strength, coordination, and memory. Gene expression of proinflammatory and anti-inflammatory cytokines was analyzed in brain tissue. Results: The combined treatment significantly improved locomotor activity, muscle strength, and memory during remyelination phases while suppressing proinflammatory gene expression and enhancing anti-inflammatory pathways in the brain. Conclusions: SH and IBD combination therapy provides enhanced anti-inflammatory and functional benefits compared with monotherapies, supporting its potential as a promising multi-target therapeutic strategy for improving functional recovery and modulating neuroinflammation during the spontaneous remyelination phase following CPZ withdrawal.