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Article

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

1
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan
2
Institute of Experimental Animal Sciences, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
3
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan
4
Department of Epilepsy, Movement Disorders and Physiology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
5
Department of Neurology, Graduate School of Medicine, Kyoto University, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(5), 1013; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051013
Received: 10 January 2019 / Revised: 14 February 2019 / Accepted: 21 February 2019 / Published: 26 February 2019
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-regulation of Kir4.1 channels in astrocytes is involved in audiogenic epileptogenesis caused by Lgi1 mutation. In addition, VPA seemed to have a prophylactic effect on Lgi1-related seizures. View Full-Text
Keywords: astrocytes; epilepsy; Kir4.1 channels; Lgi1; ADLTE; antiepileptics; valproic acid astrocytes; epilepsy; Kir4.1 channels; Lgi1; ADLTE; antiepileptics; valproic acid
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MDPI and ACS Style

Kinboshi, M.; Shimizu, S.; Mashimo, T.; Serikawa, T.; Ito, H.; Ikeda, A.; Takahashi, R.; Ohno, Y. Down-Regulation of Astrocytic Kir4.1 Channels during the Audiogenic Epileptogenesis in Leucine-Rich Glioma-Inactivated 1 (Lgi1) Mutant Rats. Int. J. Mol. Sci. 2019, 20, 1013. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051013

AMA Style

Kinboshi M, Shimizu S, Mashimo T, Serikawa T, Ito H, Ikeda A, Takahashi R, Ohno Y. 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. 2019; 20(5):1013. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051013

Chicago/Turabian Style

Kinboshi, Masato, Saki Shimizu, Tomoji Mashimo, Tadao Serikawa, Hidefumi Ito, Akio Ikeda, Ryosuke Takahashi, and Yukihiro Ohno. 2019. "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 20, no. 5: 1013. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20051013

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