Rahdar Samaneh, Basir Zahra, Tabandeh Mohammad Reza, Ghotbeddin Zohreh, Khazaeel Kaveh
Department of Basic Sciences, Division of Histology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Department of Basic Sciences, Division of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar;398(3):2651-2664. doi: 10.1007/s00210-024-03381-4. Epub 2024 Sep 9.
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system, especially the cerebellum, with numerous physical and mental symptoms. Oxidative stress caused by inflammation can play a role in the occurrence of this disease. Betaine, a natural methyl donor compound, has potent neuroprotective effects. Here, we investigated the effects of betaine on motor behavior, cerebellar histological changes, oxidative stress response, and endoplasmic reticulum stress in a cuprizone (CPZ)-induced multiple sclerosis model in male rats. Twenty Wistar adult male rats were randomly divided into four groups including control, MS, betaine-treated MS, and betaine groups. MS was induced by feeding animals with rodent chow containing 0.5% CPZ for 12 weeks. Betaine was daily administrated as 1% in drinking water for the last 6 weeks. The motor behavioral performance was evaluated by open field, rotarod, and reverse basket tests. Histological analysis of the cerebellum was performed by hematoxylin and eosin (H&E) and Cresyl violet (Nissl) staining. Oxidative stress factors (GSH, GSSG, GPX, GR, and GT) were assessed in the experimental groups and finally, the expression of ERS-associated proteins was measured using western blot analysis. Data showed that treatment with betaine could effectively prevent and reverse the adverse behavioral manifestation compared with the MS group. Betaine treatment protected cerebellar demyelination and neuron and Purkinje cell degeneration against CPZ-induced demyelination. Betaine attenuated the protein levels of ESR-related proteins in the cerebellum of MS rats and similarly increased the level of enzymes related to antioxidants in the cerebellum. Therefore, our results suggest that oral administration of betaine may be used as a novel adjunct therapy against cerebellar dysfunctions in an animal model of MS.
多发性硬化症（MS）是中枢神经系统最常见的脱髓鞘疾病，尤其是小脑，会出现众多身心症状。炎症引起的氧化应激可能在该疾病的发生中起作用。甜菜碱是一种天然的甲基供体化合物，具有强大的神经保护作用。在此，我们研究了甜菜碱对雄性大鼠 cuprizone（CPZ）诱导的多发性硬化症模型中运动行为、小脑组织学变化、氧化应激反应和内质网应激的影响。20 只成年雄性 Wistar 大鼠随机分为四组，包括对照组、MS 组、甜菜碱治疗的 MS 组和甜菜碱组。通过给动物喂食含 0.5% CPZ 的啮齿动物饲料 12 周诱导 MS。在最后 6 周，将甜菜碱以 1%的浓度每日添加到饮用水中。通过旷场试验、转棒试验和反向篮式试验评估运动行为表现。通过苏木精和伊红（H&E）染色以及甲酚紫（尼氏）染色对小脑进行组织学分析。在实验组中评估氧化应激因子（GSH、GSSG、GPX、GR 和 GT），最后，使用蛋白质印迹分析测量内质网应激相关蛋白的表达。数据表明，与 MS 组相比，甜菜碱治疗可有效预防和逆转不良行为表现。甜菜碱治疗可保护小脑免受 CPZ 诱导的脱髓鞘、神经元和浦肯野细胞变性。甜菜碱降低了 MS 大鼠小脑内质网应激相关蛋白的水平，同样增加了小脑中与抗氧化剂相关的酶的水平。因此，我们的结果表明，口服甜菜碱可能作为一种新型辅助疗法用于 MS 动物模型中对抗小脑功能障碍。
