Ameliorative effects of acetyl-L-carnitine on corpus callosum and functional recovery in demyelinated mouse model

Abstract

Aim

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system. Oxidative stress via distinct pathobiological pathways plays a pivotal role in the formation and persistence of MS lesions. Acetyl-L-carnitine (ALC) facilitates the uptake of acetyl coenzyme-A into the mitochondria by a fatty acid oxidation process. ALC could be a therapeutic antioxidant in the myelin repair process. This study explored the potential neuroprotective effects of ALC in cuprizone (CPZ) intoxicated mice.

Materials and methods

Thirty male C57BL/6 mice were divided into three groups. The control animals received a normal diet. The CPZ and CPZ + ALC groups were fed with a 0.2% cuprizone diet for 12 weeks. In the CPZ + ALC group, animals received ALC (300 mg/kg/day) from the 10^th -12^th weeks. Animals were evaluated functionally by beam walking test (BWT) weekly. Eventually, the corpus callosum (CC) was extracted for histological, biochemical, and molecular studies.

Results

BWT data showed ALC significantly improves balance and gait in the demyelinating mouse model. Histological staining represented ALC effectively increased remyelination in the CC. Biochemical evaluations demonstrated ALC decreased the malondialdehyde level with a parallel increase in the reduced glutathione and catalase activity levels in the CC. Molecular analysis revealed that ALC significantly increased the expression of oligodendrocyte transcription-2 (Olig-2) and Poly lipoproteins (Plp) genes in the CC.

Conclusions

ALC improved balance and motor coordination in the demyelinated mouse model. It may be by reducing the levels of free radicals and increasing the expression of Olig-2 and Plp as myelin-related genes.

Keywords:

• Remyelination
• cuprizone
• C57BL/6 mice
• acetyl-L-carnitine
• oxidative stress

Authors’ contribution

Sanaz Gharighnia: Investigation, Data curation, Writing – Original draft preparation; Ameneh Omidi: Conceptualization, Supervision, Funding acquisition, Formal analysis, Writing – Reviewing and Editing; Iraj Ragerdi Kashani: Conceptualization, Supervision; Mohammad Reza Sepand: Methodology; Shahram Pour beiranvand: Methodology.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval

Approval was received from the Ethics Committee of Tarbiat Modares University, Tehran, Iran (IR.MODARES.REC.1398.012). All of the procedures were carried out under the supervision of the committee and in accordance with the animal laboratory principles.

Additional information

Funding

The data presented in this paper was the principal part of the student thesis that was founded by a grant (no. Med. 78148) from the Research of Tarbiat Modares University, Faculty of Medical Sciences, Tehran, Iran.