MiRNA profiling in plasma from patients with sleep disorders reveals dysregulation of miRNAs in narcolepsy and other central hypersomnias

Abstract

miRNAs have been implicated in the pathogenesis of human diseases including neurological disorders. The aim is to address the involvement of miRNAs in the pathophysiology of central hypersomnias including narcolepsy with cataplexy and hypocretin deficiency (NC), narcolepsy without cataplexy (NwC) and idiopathic hypersomnia (IH) in comparison with healthy controls (HC). We conducted high-throughput analysis of miRNA in plasma from patients with NC, NwC and IH in comparison with HC using quantitative real-time polymerase chain reaction (qRT-PCR) panels. Data were analyzed with the following softwares: GenEx qRT-PCR data analysis, miRNA expression atlas in normal tissues and DIANA-mirPath pathway analysis. Using analysis of miRNA in plasma with qRT-PCR we identified 50, 24 and 6 miRNAs that were changed in patients with NC, NwC, IH, respectively, compared to HC. Twenty miRNA candidates which fulfilled the criteria of twofold change and p -value < 0.05 were selected for validation of miRNA changes in an independent cohort of patients. Four miRNAs were significantly changed between NC patients and HC. Levels of miR-30c, let-7f and miR- 26a were increased, whereas the level of miR-130a was decreased in NC compared to HC. The miRNAs changes were not specific for NC, since the levels of the four miRNAs were also altered in patients with NwC and IH compared with HC. The levels of four miRNAs are changed in plasma from patients with NC, NwC and IH suggesting that alterations of miRNAs can be involved in the pathophysiology of central hypersomnias. Lundbeck Foundation is acknowledged for financial support. Birte Kofoed is thanked for technical assistance.