title: Bcl-w protects hippocampus during experimental status epilepticus.
abstract: Experimentally evoked seizures can activate the intrinsic mitochondrial cell death pathway, components of which are modulated in the hippocampus of patients with temporal lobe epilepsy. Bcl-2 family proteins are critical regulators of mitochondrial dysfunction, but their significance in this setting remains primarily untested. Presently, we investigated the mitochondrial pathway and role of anti-apoptotic Bcl-2 proteins using a mouse model of seizure-induced neuronal death. Status epilepticus was evoked in mice by intra-amygdala kainic acid, causing cytochrome c release, processing of caspases 9 and 7, and death of ipsilateral hippocampal pyramidal neurons. Seizures caused a rapid decline in hippocampal Bcl-w levels not seen for either Bcl-2 or Bcl-xl. To test whether endogenous Bcl-w was functionally significant for neuronal survival, we investigated hippocampal injury after seizures in Bcl-w-deficient mice. Seizures induced significantly more hippocampal CA3 neuronal loss and DNA fragmentation in Bcl-w-deficient mice compared with wild-type mice. Quantitative electroencephalography analysis also revealed that Bcl-w-deficient mice display a neurophysiological phenotype whereby there was earlier polyspike seizure onset. Finally, we detected higher levels of Bcl-w in hippocampus from temporal lobe epilepsy patients compared with autopsy controls. These data identify Bcl-w as an endogenous neuroprotectant that may have seizure-suppressive functions.
authors: Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
authors: Brona
authors: B
authors: Murphy
authors: Mark
authors: M
authors: Dunleavy
authors: Sachiko
authors: S
authors: Shinoda
authors: Clara
authors: C
authors: Schindler
authors: Robert
authors: R
authors: Meller
authors: Carmen
authors: C
authors: Bellver-Estelles
authors: Seiji
authors: S
authors: Hatazaki
authors: Patrick
authors: P
authors: Dicker
authors: Akitaka
authors: A
authors: Yamamoto
authors: Ina
authors: I
authors: Koegel
authors: Xiangping
authors: X
authors: Chu
authors: Weizhen
authors: W
authors: Wang
authors: Zhigang
authors: Z
authors: Xiong
authors: Jochen
authors: J
authors: Prehn
authors: Roger
authors: R
authors: Simon
authors: David
authors: D
authors: Henshall
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D053179:Caspase 7 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004569:Electroencephalography; D004594:Electrophysiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007608:Kainic Acid / Q000633:toxicity; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012640:Seizures / Q000378:metabolism / Q000473:pathology; D013226:Status Epilepticus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; C491073:BCL2L2 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C101155:Bcl2l2 protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D005680:gamma-Aminobutyric Acid; D045304:Cytochromes c; D053179:Caspase 7; D053453:Caspase 9; D007608:Kainic Acid
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