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Susceptibility of pentylenetetrazole-induced seizures in mice with Cereblon gene knockout

BMB Reports 2020년 53권 9호 p.484 ~ 489
전승제, 함진실, 박철승, 이보름,
소속 상세정보
전승제 ( Jeon Seung-Je ) - Gwangju Institute of Science and Technology School of Life Sciences
함진실 ( Ham Jin-Sil ) - Gwangju Institute of Science and Technology Department of Biomedical Science and Engineering
박철승 ( Park Chul-Seung ) - Gwangju Institute of Science and Technology School of Life Sciences
이보름 ( Lee Bo-Reom ) - Gwangju Institute of Science and Technology Department of Biomedical Science and Engineering

Abstract


Epilepsy is a neurological disorder characterized by unpredictable seizures, which are bursts of electrical activity that temporarily affect the brain. Cereblon (CRBN), a DCAFs (DDB1 and CUL4-associated factors), is a well-established protein associated with human mental retardation. Being a substrate receptor of the cullin-RING E3 ubiquitin ligase (CRL) 4 complex, CRBN mediates ubiquitination of several substrates and conducts multiple biological processes. In the central nervous system, the largeconductance Ca2+-activated K+ (BKCa) channel, which is the substrate of CRBN, is an important regulator of epilepsy. Despite the functional role and importance of CRBN in the brain, direct injection of pentylenetetrazole (PTZ) to induce seizures in CRBN knock-out mice has not been challenged. In this study, we investigated the effect of PTZ in CRBN knock-out mice. Here, we demonstrate that, compared with WT mice, CRBN knock-out mice do not show the intensification of seizures by PTZ induction. Moreover, electroencephalography recordings were also performed in the brains of both WT and CRBN knockout mice to identify the absence of significant differences in the pattern of seizure activities. Consistently, immunoblot analysis for validating the protein level of the CRL4 complex containing CRBN (CRL4Crbn) in the mouse brain was carried out. Taken together, we found that the deficiency of CRBN does not affect PTZ-induced seizure.

키워드

BKCa channel; CRBN; Electroencephalography; Pentylenetetrazole; Seizure

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