期刊
NANO LETTERS
卷 22, 期 6, 页码 2381-2390出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c00025
关键词
epilepsy; tetrahedral framework nucleic acid; antiepilepticus drugs; gliosis; glutamine synthetase; AMPAR trafficking
类别
资金
- National Key R&D Program of China [2019YFA0110600]
- National Natural Science Foundation of China [81970916, 81971295, 82001216, 82171355]
- China Postdoctoral Science Foundation [2021M700699]
Nanomaterial tFNA shows potential as an antiepileptic drug by crossing the blood-brain barrier, reducing inflammation and neuronal hyperexcitability in mice, and may provide a new direction for epilepsy treatment.
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.
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