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

Abstract

Epilepsy is a neurological disorder characterized by unpredictable seizures, which are bursts of electrical activity that tempo-rarily affect the brain. Cereblon (CRBN), a DCAFs (DDB1 and CUL4associated 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 large-conductance 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, di-rect 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.