Lim Kinase1 regulates seizure activity via modulating actin dynamics.

Lim kinase1 (LIMK1) plays a vital role in dendritic spine morphogenesis and brain function. However, the mechanism of LIMK1 in epilepsy remains unclear. Our study showed that LIMK1 was upregulated in the hippocampal dentate gyrus (DG) of a pentylenetetrazol (PTZ)-kindled epilepsy rat model. Downregulation of LIMK1 reduced susceptibility to seizures in the PTZ-induced rat model, whereas combined LIMK1 knockdown and jasplakinolide treatment increased the duration of stage 4-5 seizures in PTZ-kindled rats. Via in vitro experiments, we explored the possible mechanism of LIMK1 in seizures. LIMK1 was closely related to actin depolymerization and dendritic spine maturation in Mg-free treated hippocampal neurons. Additionally, LIMK1 affected actin polymerization by regulating the level of p-cofilin. Mechanistically, our results show that LIMK1 regulates actin-mediated alterations in dendritic spine morphology in epileptic rats, which requires cofilin phosphorylation. Taken together, our results show that LIMK1 is involved in the spatial control of actin dynamics and kinase signaling in seizures, providing new insights into structural plasticity mechanisms in epilepsy.