Contrasting patterns of Bim induction and neuroprotection in Bim-deficient mice between hippocampus and neocortex after status epilepticus

Murphy, BM; Engel, T; Paucard, A; Hatazaki, S; Mouri, G; Tanaka, K; Tuffy, LP; Jimenez-Mateos, EM; Woods, I; Dunleavy, M; Bonner, HP; Meller, R; Simon, RP; Strasser, A; Prehn, JHM; Henshall, DC

Author(s): Murphy, BM; Engel, T; Paucard, A; Hatazaki, S; Mouri, G; Tanaka, K; Tuffy, LP; Jimenez-Mateos, EM; Woods, I; Dunleavy, M; Bonner, HP; Meller, R; Simon, RP; Strasser, A; Prehn, JHM; Henshall, DC;
Details: Publication Year 2010-03,Volume 17,Issue #3,Page 459-468
Journal Title: CELL DEATH AND DIFFERENTIATION
Publication Type: Journal Article
Abstract: Prolonged seizures (status epilepticus) are associated with brain region-specific regulation of apoptosis-associated signaling pathways. Bcl-2 homology domain 3-only (BH3) members of the Bcl-2 gene family are of interest as possible initiators of mitochondrial dysfunction and release of apoptogenic molecules after seizures. Previously, we showed that expression of the BH3-only protein, Bcl-2 interacting mediator of cell death (Bim), increased in the rat hippocampus but not in the neocortex after focal-onset status epilepticus. In this study, we examined Bim expression in mice and compared seizure damage between wild-type and Bim-deficient animals. Status epilepticus induced by intra-amygdala kainic acid (KA) caused extensive neuronal death within the ipsilateral hippocampal CA3 region. Hippocampal activation of factors associated with transcriptional and posttranslational activation of Bim, such as CHOP and c-Jun NH(2)-terminal kinases, was significant within 1 h. Upregulation of bim mRNA was evident after 2 h and Bim protein increased between 4 and 24 h. Hippocampal CA3 neurodegeneration was reduced in Bim-deficient mice compared with wild-type animals after seizures in vivo, and short interfering RNA molecules targeting bim reduced cell death after KA treatment of hippocampal organotypic cultures. In contrast, neocortical Bim expression declined after status epilepticus, and neocortex damage in Bim-deficient mice was comparable with that in wild-type animals. These results show region-specific differential contributions of Bim to seizure-induced neuronal death. Cell Death and Differentiation (2010) 17, 459-468; doi: 10.1038/cdd.2009.134; published online 25 September 2009
Publisher: NATURE PUBLISHING GROUP
Keywords: ENDOPLASMIC-RETICULUM STRESS; TEMPORAL-LOBE EPILEPSY; BCL-2 FAMILY-MEMBER; APOPTOSIS-INDUCING FACTOR; BH3-ONLY PROTEIN BIM; NEURONAL CELL-DEATH; PROAPOPTOTIC ACTIVITY; KAINIC ACID; RAT-BRAIN; INJURY
Publisher's Version: https://doi.org/10.1038/cdd.2009.134
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Creation Date: 2010-03-01 12:00:00