Antiepilepticus Effects of Tetrahedral Framework Nucleic Acid via Inhibition of Gliosis-Induced Downregulation of Glutamine Synthetase and Increased AMPAR Internalization in the Postsynaptic Membrane

被引：56

作者：

Zhu, Jianwei ^{[1
]}

Yang, Yuting ^{[2
]}

Ma, Wenjuan ^{[2
]}

Wang, Yangyang ^{[1
]}

Chen, Lihua ^{[1
]}

Xiong, Huan ^{[1
]}

Yin, Cheng ^{[1
]}

He, Zongze ^{[1
]}

Fu, Wei ^{[3
]}

Xu, Ruxiang ^{[1
]}

Lin, Yunfeng ^{[2
]}

机构：

[1] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Neurosurg, Chengdu 611731, Peoples R China

[2] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Natl Clin Res Ctr Oral Dis, Chengdu 610041, Peoples R China

[3] Sichuan Univ, Dept Neurosurg, West China Hosp, Chengdu 610041, Peoples R China

来源：

NANO LETTERS | 2022年 / 22卷 / 06期

基金：

中国博士后科学基金; 国家重点研发计划; 中国国家自然科学基金;

关键词：

epilepsy; tetrahedral framework nucleic acid; antiepilepticus drugs; gliosis; glutamine synthetase; AMPAR trafficking; EPILEPSY; EPILEPTOGENESIS; HIPPOCAMPUS; SEIZURES;

D O I：

10.1021/acs.nanolett.2c00025

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

More than 15 million out of 70 million patients worldwide do not respond to available antiepilepticus drugs (AEDs). With the emergence of nanomedicine, nanomaterials are increasingly being used to treat many diseases. Here, we report that tetrahedral framework nucleic acid (tFNA), an assembled nucleic acid nanoparticle, showed an excellent ability to the cross blood-brain barrier (BBB) to inhibit M1 microglial activation and A1 reactive astrogliosis in the hippocampus of mice after status epilepticus. Furthermore, tFNA inhibited the downregulation of glutamine synthetase by alleviating oxidative stress in reactive astrocytes and subsequently reduced glutamate accumulation and glutamate-mediated neuronal hyperexcitability. Meanwhile, tFNA promotes a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization in the postsynaptic membrane by regulating AMPAR endocytosis, which contributed to reduced calcium influx and ultimately reduced hyperexcitability and spontaneous epilepticus spike frequencies. These findings demonstrated tFNA as a potential AED and that nucleic acid material may be a new direction for the treatment of epilepsy.

引用

页码：2381 / 2390

页数：10