Journal Article

Betaine alleviates cerebellar endoplasmic reticulum stress and oxidative imbalance in a cuprizone model of multiple sclerosis in rat

Rahdar, Samaneh, Khazaeel, Kaveh, Ghotbeddin, Zohreh, Tabandeh, Mohammad Reza, Basir, Zahra

2025

Overview

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.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Animal models / Animals / Antioxidants - pharmacology / Behavior, Animal - drug effects / Betaine / Betaine - pharmacology / Betaine - therapeutic use / Biomedical and Life Sciences / Biomedicine / Central nervous system / Cerebellum / Cerebellum - drug effects / Cerebellum - metabolism / Cerebellum - pathology / Cuprizone / Demyelinating diseases / Demyelination / Disease Models, Animal / Drinking water / Endoplasmic reticulum / Endoplasmic Reticulum Stress - drug effects / Male / Mental disorders / Motor Activity - drug effects / Motor task performance / Multiple sclerosis / Multiple Sclerosis - chemically induced / Multiple Sclerosis - drug therapy / Multiple Sclerosis - metabolism / Multiple Sclerosis - pathology / Neuroprotection / Neuroprotective Agents - pharmacology / Neuroprotective Agents - therapeutic use / Neurosciences / Oral administration / Oxidative stress / Oxidative Stress - drug effects / Pharmacology/Toxicology / Rats / Rats, Wistar