CRMP2 regulates mossy fiber sprouting and modulates microtubule dynamics in a pilocarpine induced rat model of epilepsy

Objective: Our study aimed to investigate the role of CRMP2 in mossy fiber sprouting (MFS) using a pilocarpine-induced rat model of epilepsy.

Methods: First, the rats were sacrificed on the 1, 7, 14 and 28 day after pilocarpine injection. Quantitative Real-time PCR (qPCR) and Western blot (WB) were performed to assess mRNA and protein levels in the hippocampus and cortex. Next, shCRMP2 AAV was injected into the dentate gyrus of hippocampus to knock down CRMP2 expression. Two weeks later, the epileptic rat model was induced by pilocarpine injection. On the day of status epilepticus (SE) induction, animals in the shCtrl + EP + LCM and shCRMP2 + EP + LCM group received twice-daily intragastric administration of Lacosamide (LCM). The rats were video monitored from day 7 to 28, and were sacrificed on day 28 after pilocarpine injection for subsequent experiment.

Results: In the present study, we observed downregulation of phosphorylated CRMP2 in the hippocampus of epileptic rats. Additionally, LCM treatment reduces the expression level of CRMP2 protein in the hippocampus of these rats. Both CRMP2 knockdown and LCM treatment were found to decrease mossy fiber sprouting (MFS) in the dentate gyrus and shorten the duration of seizures in epileptic rats. Furthermore, we discovered that microtubule dynamics are reduced in the hippocampus of epileptic rats. Both CRMP2 Knockdown and LCM treatment were shown to increase the microtubule dynamics in the hippocampus of rats with epilepsy.

Conclusion: In conclusion, we demonstrated convincingly that CRMP2 regulates mossy fiber sprouting and modulates microtubule dynamics in a pilocarpine induced rat model of epilepsy.