New Discernment of Pathophysiological Aspects of Multiple Sclerosis Based On Mono Amino Oxidase (MAO) and Ion Channel Receptor 5HT3RA as Activator of T-Cells

Abstract

Background: Multiple sclerosis (MS) is a chronic, inflammatory and autoimmune disease of central nervous system. MS affects nearly 2.5 million people in the world and is twice more common in women than men. Autoimmune T-cells target the myelin sheath in central nervous system, causing inflammation, demyelination and eventual destruction of neurons. We examined changing expression of serotonin receptor (5-HT 3 R A ) as well as monoamine oxidase (MAO-A) genes in peripheral blood mononuclear cells in MS patients. Materials and methods:In this study, peripheral blood mononuclear cells (PBMC) were first isolated from 30 healthy controls and 30 volunteers with MS using Ficoll-hypaque. Total RNA was extracted and cDNA was synthesized. In this process, mRNA concentration of 5-HT 3 R A and MAO-A as target genes as well as β-actin as reference gene was compared in PBMC of healthy subjects and patients using Real-time PCR.Results: After statistical analysis of resulting data, a significant increase was observed in the expression of 5-HT 3 R A receptor gene as well as MAO-A gene in PBMC of patients with multiple sclerosis (P=0.001). Conclusion:According to previous studies on the association between serotonin level with MS importance of 5-HT 3 R A serotonin receptor in the function of this neurotransmitter as well as T-cell activation along with significant increase in the expression of 5-HT 3 R A receptor in MS patients, it can be concluded that overexpression of this receptor has a significant correlation with MS progress. On the other hand, considering the fact that monoamine oxidase is a key enzyme responsible for oxidation of serotonin in the nervous system, perhaps the body is not capable of maintaining normal level of this enzyme in MS patients. Therefore, considerable increase in MAO level may be responsible for reduced level of serotonin in MS patients, which is a likely reason for depression in these patients.

Gene expression of serotonergic markers in peripheral blood mononuclear cells of patients with late-onset Alzheimer's disease

“…In a review of the literature, no similar studies of 5-HTR2A, 5-HTR3A and MAO-A gene expression in PBMC of patients with LOAD were found, but so far the peripheral expression profiles of each of these genes (alone or in combination) have been investigated in other human disorders such as depression, multiple sclerosis, breast cancer, and allergic asthma [ 56 , 71 , 72 , 73 , 74 ]. Although only one study using [3H]LSD as a radio-ligand showed that platelet density of 5-HT2 receptors in AD patients was not significantly different from that of healthy controls [ 75 ], no similar studies were found to investigate the 5-HT receptors in other peripheral blood cells of AD patients.…”