Analysis of platelet-derived growth factor receptor A and oligodendrocyte transcription factor 2 markers following Hydroxychloroquine administration in animal induced multiple sclerosis model

Abstract

Background: It has been shown that following demyelination, Oligodendrocyte Progenitor Cells (OPCs) migrate to the lesion site and begin to proliferate, and differentiate. This study aimed to investigate the effects of Hydroxychloroquine (HCQ) on the expression of OLIG-2 and PDGFR-α markers during the myelination process.Method and Materials: C57BL/6 mice were fed cuprizone pellets for 5 weeks to induce demyelination and return to a normal diet for 1 week to stimulate remyelination. During the Phase I all of the animals except CPZ and Vehicle groups were exposed to HCQ (2.5, 10, and 100mg/kg) via drinking water. At the end of the study, animals were euthanized, perfused and the brain samples were assessed for myelination and immunohistochemistry evaluation.Results: What is remarkable is the high rate of Olig2+ cells in the groups treated with 10 and 100 mg/kg HCQ in the demyelination phase and its decreasing trend in the remyelination phase. However, there was no signi cant difference between groups during phase I and Phase II based on the percentage of olig-2+ / total cells in the corpus callosum region. The number of PDGFR-α+ cells in the group treated with 10 mg/kg HCQ was signi cant in the rst phase (pvalue<0.05).Discussion: Considering that the 100 mg/kg HCQ group had the highest level of PDGFR-α as well as the highest level of myelin repair in LFB staining, it could be inferred that it was the most effective dose in inducing proliferation and migration of OPCs.

Neuropathic-like Nociception and Spinal Cord Neuroinflammation Are Dependent on the TRPA1 Channel in Multiple Sclerosis Models in Mice

“…This transcript factor regulates myelin regeneration during chronic demyelination and represents an important marker for investigating a possible new target to restore myelination [64]. In the cuprizone model, the demyelination was related to a reduction in luxol fast blue staining and a significant reduction in the cell numbers marked by Olig2 [65]. Here, we reported a reduction in Olig2 and luxol fast blue staining in the spinal cord in PMS-and RR-EAE-induced mice, and TRPA1 deletion showed a prevention of the demyelinating process.…”