Ferulic Acid Ameliorates Cell Injuries, Cognitive and Motor Impairments in Cuprizone-Induced Demyelination Model of Multiple Sclerosis

Abstract

Objective:Ferulic acid (FA) is a phenolic compound that exhibits neuroprotective effects in the central nervous system(CNS). This study was conducted to evaluate the potential effects of FA on the cognitive and motor impairments in thecuprizone-induced demyelination model of multiple sclerosis (MS).Materials and Methods:In this experimental study, demyelination was induced in mice by feeding them with chowcontaining cuprizone (CPZ) 0.2% for 6 weeks. Mice in the control group received normal chow. Mice in the CPZ+Veh,CPZ+FA10, and CPZ+FA100 groups received saline, and FA at a dose of 0, 10, or 100 mg/kg (intraperitoneal, I.P., daily)respectively. After cognitive and motor assessments, under anaesthesia, animal brains were removed for evaluatingthe histological, apoptosis, and molecular changes.Results: The results showed that FA increased freezing behaviour in contextual (P<0.05) and cued freezing tests(P<0.05). FA also reduced the random arm entrance (P<0.01) and increased spontaneous alternations into the arms ofY-maze compared to the CPZ+Veh group (P<0.05). Time on the rotarod was improved in rats that received both dosesof FA (P<0.01). Demyelination, apoptosis, and relative mRNA expression of p53 were lower in the FA-treated groupsrelative to the CPZ+Veh group (P<0.01). In addition, FA increased mRNA expression of brain-derived neurotrophicfactor (Bdnf), Olig2, and Mbp (P<0.05) but decreased GFAP mRNA expression compared to the CPZ+Veh group(P<0.01).Conclusion: The results of this study showed that FA plays a significant neuroprotective role in CPZ models ofdemyelination by reducing neuronal apoptosis and improving oligodendrocytes (OLs) growth and differentiation.

Keywords

• apoptosis
• cuprizone
• demyelination
• ferulic acid
• oligodendrocyte