A conjoint analysis of epilepsy and migraine through network-and-pathway-based method.

BACKGROUND: Epilepsy and migraine are both considered as paroxysmal neurologic disorders. Previous studies have reported some cases with comorbidity of these two diseases. As the underlying molecular mechanism remains unclear, we performed a network-and-pathway-based method with candidate gene sets of epilepsy and migraine to explore it. METHODS: : Comparing the candidate genes between epilepsy and migraine, we identified 21 common genes. Functional enrichment analysis indicated that epilepsy and migraine are dysfunctional in the similar biological processes, such as glutamatergic transmissions, channel activities, and transporter activities. We also explored many shared pathways between these two diseases such as neuroactive ligand-receptor interaction. RESULTS: By combining systematical analysis and previous studies review, we finally identified six essential genes associated with the comorbidity of epilepsy and migraine. CONCLUSIONS: This is the first time to address the common ground of epilepsy and migraine by a systematic biology method. The present study provides a novel way to explain the potential mechanisms of these two diseases and a new set of therapeutic targets.

The Runx1/Notch1 Signaling Pathway Participates in M1/M2 Microglia Polarization in a Mouse Model of Temporal Lobe Epilepsy and in BV-2 Cells.

Microglial activation and phenotypic shift play vital roles in many neurological diseases. Runt-related transcription factor-1 (Runx1), which is localized on microglia, inhibits amoeboid microglial proliferation. Preliminary data have indicated that the interaction of Runx1 with the Notch1 pathway affects the hemogenic endothelial cell shift. However, little is known about the effect of Runx1 and the Notch1 signaling pathway on the phenotypic shift of microglia during neuroinflammation, especially in temporal lobe epilepsy (TLE). A mouse model of TLE induced by pilocarpine and the murine microglia cell line BV-2 were used in this study. The proportion of microglia was analyzed using flow cytometry. Western blot (WB) analysis and quantitative real-time polymerase chain reaction were used to analyze protein and gene transcript levels, respectively. Immunohistochemistry was used to show the distribution of Runx1. In the present study, we first found that in a male mouse model of TLE induced by pilocarpine, flow cytometry revealed a time-dependent M2-to-M1 microglial transition after status epilepticus. The dynamic expression patterns of Runx1 and the downstream Notch1/Jagged1/Hes5 signaling pathway molecules in the epileptic hippocampus were determined. Next, Runx1 knockdown by small interfering RNA in BV-2 cells strongly promoted an M2-to-M1 microglial phenotype shift and inhibited Notch1/Jagged1/Hes5 pathway expression. In conclusion, Runx1 may play a critical role in the M2-to-M1 microglial phenotype shift via the Notch1 signaling pathway during epileptogenesis in a TLE mouse model and in BV-2 cells.