Han Tao, Qin Yanyu, Mou Chenzhi, Wang Min, Jiang Meng, Liu Bin
Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University 9677 Jingshi Road, Jinan, Shandong 250021, China.
Am J Transl Res. 2016 Oct 15;8(10):4499-4509. eCollection 2016.
Seizures, which result from synchronized aberrant firing of neuronal populations, can cause long-term sequelae, such as epilepsy, cognitive and behavioral issues, in which the synaptic plasticity alteration may play an important role. Long-term potentiation (LTP) is a persistent increase in synaptic strength and is essential for learning and memory. In the present study, we first examined the alteration of cognitive impairments and synaptic plasticity in mice with seizures, then explored the underlying mechanism involving pro-inflammatory factors and PI3K/Akt pathway. The results demonstrated that: (1) PTZ-induced seizure impairs learning and memory in mice, indicated by Morris water maze test; (2) PTZ-induced seizure decreased LTP; (3) the mRNA expression of IL-1β, IL-6 and TNF-α in the hippocampus were increased in mice with seizures; (4) LTP was increased by IL-1β receptor antagonist anakinra, but not inhibitors of IL-6 or TNF-α receptor; (5) Antagonist of IL-1β receptor rescues deficits in learning and memory of mice with seizures through PI3K/Akt pathway. It is concluded that the IL-1β induced by PTZ-induced seizures may impair the synaptic plasticity alteration in hippocampus as well as learning and memory ability by PI3K/Akt signaling pathway.
癫痫发作是由神经元群体同步异常放电引起的，可导致长期后遗症，如癫痫、认知和行为问题，其中突触可塑性改变可能起重要作用。长时程增强（LTP）是突触强度的持续增加，对学习和记忆至关重要。在本研究中，我们首先检查了癫痫小鼠的认知障碍和突触可塑性的改变，然后探讨了涉及促炎因子和PI3K/Akt途径的潜在机制。结果表明：（1）通过莫里斯水迷宫试验表明，戊四氮诱导的癫痫发作损害小鼠的学习和记忆；（2）戊四氮诱导的癫痫发作降低了LTP；（3）癫痫小鼠海马中IL-1β、IL-6和TNF-α的mRNA表达增加；（4）IL-1β受体拮抗剂阿那白滞素可增加LTP，但IL-6或TNF-α受体抑制剂则不能；（5）IL-1β受体拮抗剂通过PI3K/Akt途径挽救癫痫小鼠的学习和记忆缺陷。得出的结论是，戊四氮诱导的癫痫发作所诱导的IL-1β可能通过PI3K/Akt信号通路损害海马中的突触可塑性改变以及学习和记忆能力。
