Type I interferon signaling enhances kainic acid-induced seizure severity
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, yet the role and mechanisms of type I interferon (IFN) signaling in seizure conditions remain elusive. In this study, we demonstrate that type I IFN signaling exacerbates seizure phenotypes in a kainic acid-induced seizure mouse model. We found that the absence of type I IFN signaling in Ifnar1-/- mice led to decreased neuronal excitability and microglial activation in response to kainic acid stimulation. Conversely, intracerebroventricular injection of IFN-{beta} heightened the severity of kainic acid-induced seizures. In vitro calcium imaging revealed that IFN-{beta} treatment amplified both basal and kainic acid-induced neuronal excitability, though no significant difference was observed in basal neuronal excitability between wild-type and Ifnar1-/- neurons. Furthermore, Ifnar1-/- mice exhibited reduced mTOR activation in the brain following kainic acid administration. Consistent with this finding, IFN-{beta} treatment induced mTOR activation, as indicated by S6 phosphorylation in in vitro mixed glial cultures. Taken together, these results demonstrate the critical role of type I IFN signaling in seizure pathogenesis and suggest that targeting type I IFNs could be a promising therapeutic strategy for reducing seizure severity and mitigating epilepsy.