464. COMPREHENSIVE GENE EXPRESSION ANALYSIS OF GABAERGIC NEURONS-DERIVED FROM IPS CELLS OF PATIENTS WITH FIBROMYALGIA ACCOMPANIED BY PSYCHIATRIC SYMPTOMS

Abstract Background Fibromyalgia is an intractable disease that causes chronic pain and stiffness over a wide area of the body for an unknown reason, as well as a variety of neurological and psychiatric symptoms such as sleep disorders and depression as accompanying symptoms. Based on this situation, it is thought that there may be abnormalities in the GABAergic neurons, which are closely related to psychiatric symptoms. However, the exact etiology of fibromyalgia is still unclear. On the other hand, in recent years, the development of induced pluripotent stem cell (iPS cell) technology has made it possible to induce various types of nerve cells from iPS cells, and it is hoped that this technology will be utilized to elucidate the pathogenesis of the disease. Aims & Objectives In this study, we attempted to search for disease susceptibility factors involved in the pathogenesis of fibromyalgia by focusing on GABAergic neurons subtypes and analyzing the comprehensive gene expression data obtained from GABAergic neurons derived from iPS cells of fibromyalgia patients with psychiatric symptoms. Method We established iPS cells from healthy controls and patients with fibromyalgia in accordance with ethical guidelines of the research facility. These iPS cells were differentiated into GABAergic neurons using a combination of small molecule compounds in order to have regional specificity for the forebrain. Gene expression analysis was performed according to RNA-seq. Results We found that GABAergic neurons differentiated from iPS cells were derived from the basal ganglia and had the characteristics of GABAergic neurons localized in the cerebral cortex. In addition, GABAergic neurons derived from iPS cells were a subtype that highly expressed somatostatin. Under these conditions, we performed comprehensive gene expression analysis of GABAergic neurons-derived from iPS cells of healthy control and patients with fibromyalgia. As a result, there were significant differences in gene expression changes between healthy controls and patients with fibromyalgia due to neural maturation over time during differentiation induction. Furthermore, in the fibromyalgia patient-derived GABAergic neurons, there were changes in the expression of the molecules that constitute the subtypes of GABA neurons. Discussion & Conclusions These results suggest that changes in the expression of specific genes that determine GABAergic neuronal subtypes under fibromyalgia may lead to the induction of comorbid symptoms such as depression.