Stathmin 1 regulates epileptic seizures by influencing GABA_A R-mediated inhibitory synaptic activity

Epilepsy is a common neurological disease, and approximately 30% of patients with epilepsy do not respond adequately to antiseizure medications. STMN1 (Stathmin 1) is a potent regulator of microtubule stability, and previous research has shown that STMN1 expression is increased in epileptic brain. However, the effect of STMN1 on epileptic seizures remains unclear. Our study found that STMN1 expression was associated with GABA_A receptor (GABA_AR), inhibitory GABAergic neurons and the inhibitory postsynaptic scaffold protein gephyrin. STMN1 downregulation decreased the susceptibility to epileptic seizures in a kainic acid-induced model and pentylenetetrazole-induced kindling model of epilepsy, whereas the overexpression of STMN1 showed opposite effects. More specifically, whole-cell patch-clamp recordings indicate that STMN1 regulated inhibitory synaptic transmission, potentially due to STMN1-mediated postsynaptic GABA_AR transport. These results provides the demonstration that STMN1 plays a critical role in the regulation of epileptic seizures, suggesting a molecular mechanism for new therapeutic strategies.