Modulation of MicroRNAs Linked to Pain-migraine by Ketogenic Diet (P14-007-19)
Abstract Objectives Migraine is a neurovascular disorder with complex pathophysiology. The ketogenic diet (KD) it is well recognized to treat epilepsy drug-resistant as well as other neurological disorder including migraine. Our previous study showed that six weeks of biphasic KD influences circulating microRNAs (miRs) linked to energy metabolism (Cannataro R., Perri M. et al. MicroRNA (2019) 8: 1). At the end of the study, six female obese patients self-reported to had a better outcome of pain-migraine and migraine attack. Therefore, we analyzed miRs associated with pain-migraine. Methods The KD was planned depending on the dietary diary recorded by each subject for 14 days before starting the KD program and was set with less than 30 g of carbohydrate per day. Six female obese patients in stage 1 of the Edmonton Obesity Staging System (EOSS) parameter self-reporting suffering of migraine were analyzed for miRs linked to pain-migraine. 200 microL of blood/serum was used for the extraction of miRs and their expression profile was achieved by direct hybridization using the multiplexed NanoString nCounter-flex system. In silico bioinformatics approach (using miRWalk, miR target link, and target scan) were employed to detect target genes and miRNA-regulated biological function. Results The six female obese patients whose reduce their weight during the biphasic KD program, self-reported that migraines attack disappeared only during, and not outside, the cycles of biphasic KD program. Among the 7 miRs linked to pain-migraine (Gallelli L. et al. MicroRNA (2017) 6: 152), 6 were found substantially at the same levels before and after the KD program (Table 1). Even, the brain-enriched hsa-382–5p was confirmed to be unchanged according to previous finding (Andersen H.H. et al. Mol Neurobiol. (2016) 53: 1494) (Table 1). While the has-miR-590–5p and the emerging hsa -miR-660–3p were strongly affected by KD (Fig 1A-B). The validated target gene of this three latter miRs were 3, 2 and any respectively (Table 2). Conclusions KD thought miRs modulation could contribute to restore brain excitability and metabolism and to counteract neuroinflammation and pain-migraine, although the precise mechanism is still unclear. Funding Sources Fund was obtained from Calabria Regional Council POR FSE 2007/2013 to EC. Supporting Tables, Images and/or Graphs