Type

Journal Article

Authors

David Henshall
Roger Simon
Jochen Prehn
Zhigang Xiong
Weizhen Wang
Xiangping Chu
Ina Koegel
Akitaka Yamamoto
Patrick Dicker
Seiji Hatazaki
and 6 others

Subjects

Biochemistry

Topics
toxicity bcl2l2 protein mouse mice mutant strains genetics seizures proteins hippocampus metabolism status epilepticus neurons membrane proteins pathology physiology kainic acid mitochondria apoptosis regulatory proteins dna fragmentation animals electroencephalography physiopathology bcl2l2 protein human apoptosis gamma aminobutyric acid mice bcl 2 like protein 11 caspase 7 electrophysiology proto oncogene proteins cytochromes c humans caspase 9

Bcl-w protects hippocampus during experimental status epilepticus. (2007)

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.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David Henshall, Roger Simon, Jochen Prehn, Zhigang Xiong, Weizhen Wang, Xiangping Chu, Ina Koegel, Akitaka Yamamoto, Patrick Dicker, Seiji Hatazaki and 6 others

Experts in our system

1
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
2
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
3
Patrick Dicker
Royal College of Surgeons in Ireland
Total Publications: 95