Vezatin regulates seizures by controlling AMPAR-mediated synaptic activity.
Vezatin regulates seizures by controlling AMPAR-mediated synaptic activity.
复制标题
Vezatin 通过控制 AMPAR 介导的突触活动来调节癫痫发作
DOI：
10.1038/s41419-021-04233-2
复制
发表时间：
2021-10-12
影响因子：
9
通讯作者：
Xu T
中科院分区：
文献类型：
--
作者：
Wang Y;Yuan J;Yu X;Liu X;Tan C;Chen Y;Xu T
虽然许多研究已经探讨了癫痫的发病机制，但仍不清楚，值得进一步研究。Vezatin是一种参与神经元突触传递（NST）的突触调节蛋白。然而，vezatin在癫痫中的作用仍然未知。因此，本研究的目的是探讨vezatin在癫痫中的潜在作用。在这项研究中，vezatin表达增加海马组织毛果芸香碱（PILO）诱导的癫痫小鼠和无镁培养基诱导的体外癫痫样模型。Vezatin敲低抑制PILO诱导的癫痫小鼠的癫痫发作活动。机制上，vezatin敲低抑制癫痫小鼠中AMPAR介导的突触事件，并下调AMPAR GluA 1亚基（GluA 1）的表面表达。有趣的是，vezatin敲低降低了GluA 1在丝氨酸845处的磷酸化，并降低了蛋白激酶A（PKA）磷酸化;当PKA磷酸化被H-89（PKA磷酸化的选择性抑制剂）体外抑制时，vezatin敲低对降低GluA 1在丝氨酸845处的磷酸化和GluA 1的表面表达的影响被阻断。最后，我们研究了颞叶癫痫（TLE）患者脑组织中vezatin的表达模式，发现TLE患者的vezatin表达也增加。总之，vezatin表达模式在癫痫患者中是异常的，并且vezatin通过影响AMPAR介导的NST和GluA 1的表面表达来调节癫痫发作活动，GluA 1参与PKA介导的GluA 1丝氨酸845磷酸化，表明vezatin介导的癫痫发作调节代表癫痫的新靶点。
Although many studies have explored the mechanism of epilepsy, it remains unclear and deserves further investigation. Vezatin has been reported to be a synaptic regulatory protein involved in regulating neuronal synaptic transmission (NST). However, the role of vezatin in epilepsy remains unknown. Therefore, the aims of this study are to investigate the underlying roles of vezatin in epilepsy. In this study, vezatin expression was increased in hippocampal tissues from pilocarpine (PILO)-induced epileptic mice and a Mg2+-free medium-induced in vitro seizure-like model. Vezatin knockdown suppressed seizure activity in PILO-induced epileptic mice. Mechanistically, vezatin knockdown suppressed AMPAR-mediated synaptic events in epileptic mice and downregulated the surface expression of the AMPAR GluA1 subunit (GluA1). Interestingly, vezatin knockdown decreased the phosphorylation of GluA1 at serine 845 and reduced protein kinase A (PKA) phosphorylation; when PKA phosphorylation was suppressed by H-89 (a selective inhibitor of PKA phosphorylation) in vitro, the effects of vezatin knockdown on reducing the phosphorylation of GluA1 at serine 845 and the surface expression of GluA1 were blocked. Finally, we investigated the pattern of vezatin in brain tissues from patients with temporal lobe epilepsy (TLE), and we found that vezatin expression was also increased in patients with TLE. In summary, the vezatin expression pattern is abnormal in individuals with epilepsy, and vezatin regulates seizure activity by affecting AMPAR-mediated NST and the surface expression of GluA1, which is involved in PKA-mediated phosphorylation of GluA1 at serine 845, indicating that vezatin-mediated regulation of epileptic seizures represents a novel target for epilepsy.
登录
查看更多内容
影响因子：
11.2
作者：
Rajasekaran, Karthik;Todorovic, Marko;Kapur, Jaideep
通讯作者：
Kapur, Jaideep
影响因子：
2.9
作者：
Huang, Hao;Li, Ruohan;Chen, Yangmei
通讯作者：
Chen, Yangmei
影响因子：
7.6
作者：
Cabanero, David;Baker, Alyssa;Moron, Jose A.
通讯作者：
Moron, Jose A.
影响因子：
4.1
作者：
Navidhamidi, Mojdeh;Ghasemi, Maedeh;Mehranfard, Nasrin
通讯作者：
Mehranfard, Nasrin
DOI：
10.1016/j.mcn.2018.05.002
发表时间：
2018-09
期刊：
Molecular and cellular neurosciences
影响因子：
--
作者：
Scheefhals N;MacGillavry HD
通讯作者：
MacGillavry HD