Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou province 563003, China.
Department of Neurology, The Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, Guizhou province 563003, China.
J Chem Neuroanat. 2023 Sep;131:102289. doi: 10.1016/j.jchemneu.2023.102289. Epub 2023 May 17.
Epilepsy is a common chronic brain disease. Despite the availability of various anti-seizure drugs, approximately 30 % of patients do not respond to treatment. Recent research suggests that Kalirin plays a role in regulating neurological function. However, the pathogenesis of Kalirin in epileptic seizures remains unclear. This study aims to investigate the role and mechanism of Kalirin in epileptogenesis.
An epileptic model was induced by intraperitoneal injection of pentylenetetrazole (PTZ). Endogenous Kalirin was inhibited using shRNA. The expression of Kalirin, Rac1, and Cdc42 in the hippocampal CA1 region was measured using Western blotting. Spine and synaptic structures were examined using Golgi staining and electron microscopy. Moreover, the necrotic neurons in CA1 were examined using HE staining.
The results indicated that the epileptic score increased in epileptic animals, while inhibition of Kalirin decreased the epileptic scores and increased the latent period of the first seizure attack. Inhibition of Kalirin attenuated the increases in Rac1 expression, dendritic spine density, and synaptic vesicle number in the CA1 region induced by PTZ. However, the increase in Cdc42 expression was not affected by the inhibition of Kalirin.
This study suggests that Kalirin is involved in the development of seizures by modulating the activity of Rac1, providing a novel anti-epileptic target.
癫痫是一种常见的慢性脑部疾病。尽管有各种抗癫痫药物可供使用，但约 30%的患者对治疗无反应。最近的研究表明，Kalirin 在调节神经功能方面发挥作用。然而，Kalirin 在癫痫发作中的发病机制尚不清楚。本研究旨在探讨 Kalirin 在癫痫发生中的作用和机制。
通过腹腔注射戊四氮（PTZ）诱导癫痫模型。使用 shRNA 抑制内源性 Kalirin。使用 Western blot 测定海马 CA1 区 Kalirin、Rac1 和 Cdc42 的表达。使用高尔基染色和电子显微镜检查棘突和突触结构。此外，使用 HE 染色检查 CA1 中的坏死神经元。
结果表明，癫痫动物的癫痫评分增加，而 Kalirin 的抑制降低了癫痫评分并增加了首次癫痫发作的潜伏期。PTZ 诱导的 Rac1 表达、树突棘密度和突触囊泡数量的增加在 Kalirin 抑制后减弱。然而，Cdc42 表达的增加不受 Kalirin 抑制的影响。
本研究表明，Kalirin 通过调节 Rac1 的活性参与癫痫发作的发生，为新的抗癫痫靶点提供了依据。
