Type

Journal Article

Authors

D C Henshall
J H M Prehn
A Caballero-Caballero
E M Jimenez-Mateos
K Tanaka
T Engel

Subjects

Biochemistry

Topics
ca3 region hippocampal metabolism seizures electroencephalography phenotype toxicity animals mice knockout drug effects genetics kainic acid neuropeptide y apoptosis neurons physiopathology tumor suppressor protein p53 chemically induced mice status epilepticus

Loss of p53 results in protracted electrographic seizures and development of an aggravated epileptic phenotype following status epilepticus. (2010)

Abstract The p53 tumor suppressor is a multifunctional protein, which regulates cell cycle, differentiation, DNA repair and apoptosis. Experimental seizures up-regulate p53 in the brain, and acute seizure-induced neuronal death can be reduced by genetic deletion or pharmacologic inhibition of p53. However, few long-term functional consequences of p53 deficiency have been explored. Here, we investigated the development of epilepsy triggered by status epilepticus in wild-type and p53-deficient mice. Analysis of electroencephalogram (EEG) recordings during status epilepticus induced by intra-amygdala kainic acid (KA) showed that seizures lasted significantly longer in p53-deficient mice compared with wild-type animals. Nevertheless, neuronal death in the hippocampal CA3 subfield and the neocortex was significantly reduced at 72 h in p53-deficient mice. Long-term continuous EEG telemetry recordings after status epilepticus determined that the sum duration of spontaneous seizures was significantly longer in p53-deficient compared with wild-type mice. Hippocampal damage and neuropeptide Y distribution at the end of chronic recordings was found to be similar between p53-deficient and wild-type mice. The present study identifies protracted KA-induced electrographic status as a novel outcome of p53 deficiency and shows that the absence of p53 leads to an exacerbated epileptic phenotype. Accordingly, targeting p53 to protect against status epilepticus or related neurologic insults may be offset by deleterious consequences of reduced p53 function during epileptogenesis or in chronic epilepsy.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

D C Henshall, J H M Prehn, A Caballero-Caballero, E M Jimenez-Mateos, K Tanaka, T 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
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55
 
4
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66