Protective impacts of erythropoietin on myelinization of oligodendrocytes and schwann cells in CNS and PNS following cuprizone-induced multiple sclerosis- histology, molecular, and functional studies

Jafar Mirzaie; Amir Raoofi; Zahra Jamalpoor; Akram Nezhadi; Rahim Golmohammadi

doi:10.1016/j.jchemneu.2020.101750

Protective impacts of erythropoietin on myelinization of oligodendrocytes and schwann cells in CNS and PNS following cuprizone-induced multiple sclerosis- histology, molecular, and functional studies

J Chem Neuroanat. 2020 Jan 16:104:101750. doi: 10.1016/j.jchemneu.2020.101750. Online ahead of print.

Authors

Jafar Mirzaie¹, Amir Raoofi², Zahra Jamalpoor³, Akram Nezhadi⁴, Rahim Golmohammadi⁵

Affiliations

¹ Neuroscience Research Center, Aja University of Medical Sciences, Tehran, Iran.
² Leishmaniasis Research Center, Department of Anatomy, Sabzevar University of Medical Sciences, Sabzevar, Iran.
³ Trauma Research Center, Aja University of Medical Sciences, Tehran, Iran.
⁴ Neuroscience Research Center, Aja University of Medical Sciences, Tehran, Iran. Electronic address: Akram.nezhadi@gmail.com.
⁵ Cellular and Molecular Research Center, Department of Anatomical Sciences, Sabzevar University of Medical Sciences, Sabzevar, Iran.

PMID: 31954768
DOI: 10.1016/j.jchemneu.2020.101750

Abstract

Background: Multiple sclerosis (MS) is known as one of the chronic inflammatory diseases characterized by lesions in the central nervous system (CNS) and peripheral nervous system(PNS) resulting in serious cognitive or physical disabilities as well as neurological disorders. Thus, protective effects of erythropoietin(EPO) on myelinization of oligodendrocytes and schwann cells respectively in CNS and PNS following MS induced by cuprizone (CPZ) administration in young female mice.

Methodology: To meet the objectives of this study; a chow with 0.2 % CPZ was used to feed young female C57BL/6 J mice for six weeks. After three weeks, EPO (5000 IU/kg body weight) was administered via daily intra-peritoneal injection for simultaneous treatment of the mice. Measurement of latency and amplitude of the compound muscle action potential (CMAP) of gastrocnemius muscle was also performed every week during a six-week demyelination interval, and then examinations were fulfilled on the histological sections of the brain and sciatic nerve. Therefore, we focused on the removal of the sciatic and sciatic nerve specimens and analysis of the use of the stereological procedures, western blot, immuno-histochemistry, and gene expression.

Results: According to the results of this study, MBP levels increased in oligodendrocytes (OLs) in the treated mice. Moreover, EPO could concurrently enhance motor coordination and muscle activity. Analysis showed the significant enhancement of the gene expression of MBP, MAG, and S100, as well as stereological variables in the treatment group in comparison with the cuprizone (CPZ) group.

Conclusion: Findings could help further understand the alleviation of the detrimental impacts of CPZ using the OLs that would be capable of increasing the level of S100, MAG, and MBP.

Keywords: CNS; Cuprizone; Demyelination; Multiple sclerosis; PNS.