Analysis of changes in the expression of dopamine-related genes in fibromyalgia patient specific-iPS cell derived-dopaminergic neurons

Abstract

Fibromyalgia (FM) is a common and chronic syndrome that causes bodily pain and mental distress. The cause of FM is largely unknown, but it is expected that changes in dopamine (DA) transmission may be involved in these symptoms. In the present study, to investigate the pathophysiological mechanisms of FM, we applied for the stem cell technology using induced pluripotent stem cells (iPSCs). We differentiated iPSCs derived from FM patients into DA neurons following previous methods. Most of the differentiated cells derived from control and FM-specific iPSCs were labeled by antibodies to βⅢ-tubulin (a neuron-specific marker) and tyrosine hydroxylase (TH) (a DA neuronal marker). Under the present condition, we performed the gene expression analysis of DA neurons derived from control or FM-specific iPSCs. We focused on the possible changes in the expression of DA synthesis or metabolism-related genes among the mRNAs changed in FM patients. With no change in tyrosine hydroxylase (TH), dopa decarboxylase (DDC) and monoamine oxidase B (MAOB), the expression of catechol-O-methyltransferase (COMT) was significantly increased in FM-specific iPSC-derived DA neurons. These finding indicate that alterations of DA metabolism in FM-derived DA neurons may contribute, at least in part, to psychiatric and pain symptoms in FM patients.