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 ( D DB1 and C UL4 a ssociated f actors), 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 Ca 2+ -activated K + (BK Ca ) 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 (CRL4 Crbn ) in the mouse brain was carried out. Taken together, we found that the deficiency of CRBN does not affect PTZ-induced seizure.

Thalidomide Attenuates Epileptogenesis and Seizures by Decreasing Brain Inflammation in Lithium Pilocarpine Rat Model

“…However, there is no evidence to associate CRBN with epilepsy, the anti-inflammatory or anti-ictogenic effects of the drug. In fact, the lack of CRBN in CRBN KO mice does not affect PTZ-induced seizures in these animals [ 74 ].…”

Ablation of CRBN induces loss of type I collagen and SCH in mouse skin by fibroblast senescence via the p38 MAPK pathway

“…CRBN KO mice have been characterized in multiple phenotypical contexts. A series of studies elucidating the physiological function of CRBN has also been reported in various disease models or under specific challenges [ 15 , 24 , 29 – 31 ]. The deficiency of CRBN has exhibited protective effects or positive influence under various adverse challenges in vivo .…”