Role and mechanism of EphB3 in epileptic seizures and epileptogenesis through Kalirin

作者全名："Huang, Hao; Chen, Ling; Yuan, Jinxian; Zhang, Haiqing; Yang, Juan; Xu, Zucai; Chen, Yangmei"

作者地址："[Huang, Hao; Yuan, Jinxian; Chen, Yangmei] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, 74 Linjiang Rd, Chongqing 400010, Peoples R China; [Huang, Hao; Chen, Ling; Zhang, Haiqing; Yang, Juan; Xu, Zucai] Zunyi Med Univ, Affiliated Hosp, Dept Neurol, 149 Dalian Rd, Zunyi 563003, Guizhou, Peoples R China"

通信作者："Chen, YM (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, 74 Linjiang Rd, Chongqing 400010, Peoples R China.; Xu, ZC (通讯作者)，Zunyi Med Univ, Affiliated Hosp, Dept Neurol, 149 Dalian Rd, Zunyi 563003, Guizhou, Peoples R China."

来源：MOLECULAR AND CELLULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001165865800001

JCR分区：Q3

影响因子：2.6

年份：2024

卷号：128

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：EphB3; Kalirin; Epilepsy; Action potential; Neuronal excitability; Dendritic spines

摘要："Background: The EphB receptor tyrosine kinase family participates in intricate signaling pathways that orchestrate neural networks, guide neuronal axon development, and modulate synaptic plasticity through interactions with surface-bound ephrinB ligands. Additionally, Kalirin, a Rho guanine nucleotide exchange factor, is notably expressed in the postsynaptic membrane of excitatory neurons and plays a role in synaptic morphogenesis. This study postulates that Kalirin may act as a downstream effector of EphB3 in epilepsy. This investigation focuses on understanding the link between EphB3 and epilepsy. Materials and methods: Chronic seizure models using LiCl-pilocarpine (LiCl/Pilo) and pentylenetetrazol were developed in rats. Neuronal excitability was gauged through whole-cell patch clamp recordings on rat hippocampal slices. Real-time PCR determined Kalirin's mRNA expression, and Western blotting was employed to quantify EphB3 and Kalirin protein levels. Moreover, dendritic spine density in epileptic rats was evaluated using Golgi staining. Results: Modulation of EphB3 functionality influenced acute seizure severity, latency duration, and frequency of spontaneous recurrent seizures. Golgi staining disclosed an EphB3-driven alteration in dendritic spine density within the hippocampus of epileptic rats, underscoring its pivotal role in the reconfiguration of hippocampal neural circuits. Furthermore, our data propose Kalirin as a prospective downstream mediator of the EphB3 receptor. Conclusions: Our findings elucidate that EphB3 impacts the action potential dynamics in isolated rat hippocampal slices and alters dendritic spine density in the inner molecular layer of epileptic rat hippocampi, likely through Kalirin-mediated pathways. This hints at EphB3's significant role in shaping excitatory circuit loops and recurrent seizure activity via Kalirin."

基金机构："National Natural Science Foundation of China [81760247, 82171450]"

基金资助正文："<B>Funding</B> This research was supported by grants from the National Natural Science Foundation of China (Nos. 81760247, 82171450) ."