Type

Journal Article

Authors

David C Henshall
Jochen H M Prehn
Ina Woods
Caoimhín G Concannon
Eva M Jimenez-Mateos
Seiji Hatazaki
Brona M Murphy
Tobias Engel

Subjects

Biochemistry

Topics
antagonists inhibitors apoptosis regulatory proteins analogs derivatives genetics mice mutant strains signal transduction pathology status epilepticus male physiology pharmacology toluene mice inbred c57bl blotting western benzothiazoles tumor suppressor protein p53 physiopathology animals epilepsy mice polymerase chain reaction puma protein mouse metabolism hippocampus genotype tumor suppressor proteins pifithrin

Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma. (2009)

Abstract The functional significance of neuronal death for pathogenesis of epilepsy and the underlying molecular mechanisms thereof remain incompletely understood. The p53 transcription factor has been implicated in seizure damage, but its target genes and the influence of cell death under its control on epilepsy development are unknown. In the present study, we report that status epilepticus (SE) triggered by intra-amygdala kainic acid in mice causes rapid p53 accumulation and subsequent hippocampal damage. Expression of p53-up-regulated mediator of apoptosis (Puma), a proapoptotic Bcl-2 homology domain 3-only protein under p53 control, was increased within a few hours of SE. Induction of Puma was blocked by pharmacologic inhibition of p53, and hippocampal damage was also reduced. Puma induction was also blocked in p53-deficient mice subject to SE. Compared to Puma-expressing mice, Puma-deficient mice had significantly smaller hippocampal lesions after SE. Long-term, continuous telemetric EEG monitoring revealed a approximately 60% reduction in the frequency of epileptic seizures in the Puma-deficient mice compared to Puma-expressing mice. These are the first data showing genetic deletion of a proapoptotic protein acting acutely to influence neuronal death subsequently alters the phenotype of epilepsy in the long-term, supporting the concept that apoptotic pathway activation is a trigger of epileptogenesis.-Engel, T., Murphy, B. M., Hatazaki, S., Jimenez-Mateos, E. M., Concannon, C. G., Woods, I., Prehn, J. H. M., Henshall, D. C. Reduced hippocampal damage and epileptic seizures after status epilepticus in mice lacking proapoptotic Puma.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

David C Henshall, Jochen H M Prehn, Ina Woods, Caoimhín G Concannon, Eva M Jimenez-Mateos, Seiji Hatazaki, Brona M Murphy, Tobias Engel

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
Ina Woods
Royal College of Surgeons in Ireland
Total Publications: 16
 
4
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
5
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55
 
6
Brona M Murphy
Royal College of Surgeons in Ireland
Total Publications: 14
 
7
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66