Expression analysis of different nicotinic acetylcholine receptors genes and investigation of the effects of dimethyl fumarate administration on these changes in relapsing remitting multiple sclerosis (RRMS) patients

Abstract

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) in which demyelination and neurodegeneration occur. The immune system of MS patients is characterized by a disturbance in the balance between pro- and anti-inflammatory immune cells, in which the innate and acquired immune systems are involved. Dimethyl fumarate (DMF) was licensed in 2013 as a first-line oral treatment for relapsing-remitting (RR) MS patients. DMF alters the phenotype of circulating immune cells and induces lymphopenia in MS patients. The nicotinic acetylcholine receptor is a transmembrane allosteric protein that mediates the transmission of chemoelectric signals throughout the nervous system by opening an intrinsic ion channel. The aim of this study is to investigate the effects of DMF drug administration on the gene expression profile of nicotinic receptors in patients with relapsing-remitting multiple sclerosis. Methods: Faycol was used to extract PBMCs. After the isolation of PBMCs, cellular RNA was extracted using Trizol and cDNA was synthesized from the cDNA synthesis kit. Then, using quantitative real-time PCR, changes in the expression profile of different genes of different nicotinic receptors including beta two, alpha five, alpha seven, alpha nine and alpha ten subunits were studied. Results: The results of the experiment showed that the expression level of beta 2 and alpha 9 subionite in the samples of the group receiving DMF drug was significantly reduced compared to the group without receiving the drug. Also, the mRNA expression of subunit alpha 10 in the patient group has significantly decreased in comparison to the patient group and also in the comparison of the receiving group with the group without medication.