Knockdown of SIK3 in the CA1 Region can Reduce Seizure Susceptibility in Mice by Inhibiting Decreases in GABA A R α1 Expression.

Autor: Jiang ZF; Dalian Medical University, Dalian, 116044, Liaoning, China. jzf-1001@163.com.; Department of Neurosurgery, the Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou, Dalian, 116023, Liaoning, China. jzf-1001@163.com., Xuan LN; Dalian Medical University, Dalian, 116044, Liaoning, China., Sun XW; East China Normal University, Shanghai, 200241, China., Liu SB; Dalian Medical University, Dalian, 116044, Liaoning, China., Yin J; Dalian Medical University, Dalian, 116044, Liaoning, China. jyin@dmu.edu.cn.; Department of Neurosurgery, the Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou, Dalian, 116023, Liaoning, China. jyin@dmu.edu.cn.
Jazyk: angličtina
Zdroj: Molecular neurobiology [Mol Neurobiol] 2024 Mar; Vol. 61 (3), pp. 1404-1416. Date of Electronic Publication: 2023 Sep 16.
DOI: 10.1007/s12035-023-03630-2
Abstrakt: Imbalance between excitation and inhibition is an important cause of epilepsy. Salt-inducible kinase 1 (SIK1) gene mutation can cause epilepsy. In this study, we first found that the expression of SIK3 is increased after epilepsy. Furthermore, the role of SIK3 in epilepsy was explored. In cultured hippocampal neurons, we used Pterosin B, a selective SIK3 inhibitor that can inhibit epileptiform discharges induced by the convulsant drug cyclothiazide (a positive allosteric modulator of AMPA receptors, CTZ). Knockdown of SIK3 inhibited epileptiform discharges and increased the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). In mice, knockdown of SIK3 reduced epilepsy susceptibility in a pentylenetetrazole (a GABA A receptor antagonist, PTZ) acute kindling experiment and increased the expression of GABA A receptor α1. In conclusion, our results suggest that blockade or knockdown of SIK3 can inhibit epileptiform discharges and that SIK3 has the potential to be a novel target for epilepsy treatment.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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