Betaine alleviates deficits in motor behavior, neurotoxic effects, and neuroinflammatory responses in a rat model of demyelination.

Multiple sclerosis (MS) is characterized as a chronic inflammatory demyelinating neurodegenerative disorder that leads to the deterioration of the myelin sheath and the loss of axons. Betaine, a trimethylglycine compound, is recognized for its ability to penetrate the blood-brain barrier (BBB) and exhibits properties that are antioxidant, anti-inflammatory, and neuroprotective. The cuprizone (CPZ) model serves as an effective tool for investigating the processes of demyelination and remyelination associated with MS. In our research, we examined the protective and therapeutic effects of betaine in a rat model of MS induced by CPZ. The experimental protocol involved administering 600 mg/kg of CPZ orally for 7 days, followed by 2 weeks with 200 mg/kg of CPZ. The protective group received a combination of betaine (1 g/kg/day, orally) and CPZ (200 mg/kg/day), while the therapeutic group was treated with CPZ (600 mg/kg) alongside betaine for three weeks. Behavioral assessments were conducted using inverted screen and rotarod tests to measure balance, motor coordination, and grasping ability. Following these evaluations, the rats were euthanized for analysis of oxidative stress and inflammatory biomarkers, toluidine blue staining, transmission electron microscopy (TEM) imaging, and myelin basic protein (MBP) immunostaining of the corpus callosum (CC). The results indicated that betaine significantly enhanced balance, motor coordination, and grasping ability, while decreasing oxidative stress, inhibiting interleukin (IL)-4 and IL-17 levels, and reversing the demyelination caused by CPZ. Notably, betaine also mitigated the increase in homocysteine (Hcy) levels and facilitated remyelination, evidenced by the presence of normal compacted myelin and increased expression of MBP in the CC. This study substantiates the remyelinating effects of betaine in the context of CPZ-induced demyelination. It suggests that it may contribute to the repair of myelin through the modulation of behavioral deficits, oxidative stress, neuroinflammation, ultrastructural changes, and MBP expression levels, indicating its potential as a complementary therapeutic agent in the management of MS.