期刊
MOLECULAR NEUROBIOLOGY
卷 -, 期 -, 页码 -出版社
SPRINGER
DOI: 10.1007/s12035-023-03630-2
关键词
Epilepsy; SIK3; GABA(A)R alpha 1
The imbalance between excitation and inhibition is an important cause of epilepsy. This study found that the expression of the SIK3 gene increased in epilepsy, and blocking or silencing SIK3 can inhibit epileptic discharges, making it a potential novel target for epilepsy treatment.
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 alpha 1. 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.
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