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

Document Type : Original Article


1 Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

2 Department of Anatomical Sciences, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

3 Department of Animal Biotechnology, Cell Science Research Centre, Royan Institute for Biotechnology, Isfahan, Iran


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 the
cuprizone-induced demyelination model of multiple sclerosis (MS).

Materials and Methods:
In this experimental study, demyelination was induced in mice by feeding them with chow
containing 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 evaluating
the histological, apoptosis, and molecular changes.

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 of
Y-maze compared to the CPZ+Veh group (P<0.05). Time on the rotarod was improved in rats that received both doses
of FA (P<0.01). Demyelination, apoptosis, and relative mRNA expression of p53 were lower in the FA-treated groups
relative to the CPZ+Veh group (P<0.01). In addition, FA increased mRNA expression of brain-derived neurotrophic
factor (Bdnf), Olig2, and Mbp (P<0.05) but decreased GFAP mRNA expression compared to the CPZ+Veh group

The results of this study showed that FA plays a significant neuroprotective role in CPZ models of
demyelination by reducing neuronal apoptosis and improving oligodendrocytes (OLs) growth and differentiation.


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