The effect of IL-1β on synaptophysin expression and electrophysiology of hippocampal neurons through the PI3K/Akt/mTOR signaling pathway in a rat model of mesial temporal lobe epilepsy

Background: The inflammation induced by interleukin-1 beta (IL-1 beta) is a critical factor in the pathogenesis of mesial temporal lobe epilepsy (MTLE). Synaptophysin (SYN) and other changes, including neuron electrophysiology, participate in the pathophysiological processes of MTLE. Phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway may play a critical role in regulating SYN expression and electrophysiology of hippocampal neurons. Methods: We used lithium-pilocarpine-treated rats as model of human MTLE, detecting epileptic seizures with digital video-EEG, and evaluating the proteins related to the PI3K/Akt/mTOR signaling pathway by western blot (WB). Then, we cultured primary neuron and established a neuronal epilepsy model using Mg2+-free media. Immunocytochemistry and WB were used to investigate SYN expression, and whole-cell current clamp recording techniques were used to detect the electrophysiological properties of cultured neurons. Results: We have demonstrated that IL-1 beta can activate the PI3K/Akt/mTOR signaling pathway in primary hippocampal neurons, and we speculate that IL-1 beta may affect SYN expression and neuron electrophysiology through PI3K/Akt/mTOR signaling pathway. Conclusion: We confirmed that IL-1 beta stimulated SYN expression and epileptiform discharges, and that blocking the PI3K/Akt/mTOR pathway alleviated these phenomena. Therefore, activation of the PI3K/Akt/mTOR signaling pathway by IL-1 beta contributes to the pathogenesis of MTLE, and modulating this pathway is a promising strategy of study for therapies to prevent or reverse the cellular and molecular mechanisms of epileptogenesis in MTLE.