Down-Regulation of Astrocytic Kir4.1 Channels during the Audiogenic Epileptogenesis in Leucine-Rich Glioma-Inactivated 1 (Lgi1 ) Mutant Rats

International Journal of Molecular Sciences
Masato KinboshiYukihiro Ohno

Abstract

The dysfunction of astrocytic inwardly rectifying potassium (Kir) 4.1 channels, which mediate the spatial potassium-buffering function of astrocytes, is known to be involved in the development of epilepsy. Here, we analyzed the Kir4.1 expressional changes in Leucine-Rich Glioma-Inactivated 1 (Lgi1) mutant rats, which is a model of autosomal dominant lateral temporal lobe epilepsy in humans, to clarify the role of astrocytic Kir4.1 channels in Lgi1-related epileptogenesis. Priming acoustic stimulation (at postnatal day 16) conferred seizure susceptibility on Lgi1 mutant rats, which evoked audiogenic seizures with test stimulation at eight weeks. In the seizure-susceptible Lgi1 mutant rats (before test stimulation), astrocytic Kir4.1 expression was down-regulated region-specifically in the cerebral cortex, hippocampus, and amygdala. In addition, prophylactic treatments of Lgi1 mutant rats with valproic acid (VPA, 30 mg/kg and 200 mg/kg) for two weeks prevented both the development of seizure susceptibility and the down-regulation of Kir4.1 expression in astrocytes. The present study demonstrated for the first time that the astrocytic Kir4.1 expression was reduced in the Lgi1-related seizure model, suggesting that the down-regulat...Continue Reading

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Citations

Feb 19, 2020·Molecular Membrane Biology·Jia LiuWei Zou
Sep 10, 2020·International Journal of Molecular Sciences·Akari TakaiTomohiro Chiyonobu
Jan 12, 2021·Frontiers in Neurology·Masato KinboshiYukihiro Ohno
Oct 30, 2021·Journal of Neuroscience Research·Enes AkyuzYam Nath Paudel

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Methods Mentioned

BETA
genotyping
PCR
electrophoresis

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