Dynamic changes of proteases and protease inhibitors revealed by microarray analysis in CA3 and entorhinal cortex during epileptogenesis in the rat.
We investigated expression of genes involved in the proteolytic process during epileptogenesis in a rat model of temporal lobe epilepsy (TLE). In a previous microarray study we found prominent activation of this process, which reached highest expression during the acute and latent phase (1 week after SE) in CA3 and entorhinal cortex (EC). Detailed analysis shows differences in dynamics of the changes of several protease genes such as cathepsins, caspases, matrix metalloproteinases, and plasminogen activators. Most genes were acutely upregulated while others were mainly activated during the latent phase. Interestingly several proteolytic genes were still elevated in the chronic epileptic phase. Various protease inhibitors followed a similar time course. The identification of changes in the activation of genes involved in proteolysis at critical phases during epileptogenesis could point to potential time specific targets for intervention. The fact that several proteolytic genes were still activated in the chronic epileptic phase makes them interesting candidates to modify and slow down seizure progression.
Gorter
Jan A
JA
Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan, Amsterdam, The Netherlands. gorter@science.uva.nl
Van Vliet
Erwin A
EA
Rauwerda
Han
H
Breit
Timo
T
Stad
Robert
R
van Schaik
Linda
L
Vreugdenhil
Erno
E
Redeker
Sandra
S
Hendriksen
Erik
E
Aronica
Eleonora
E
Lopes da Silva
Fernando H
FH
Wadman
Wytse J
WJ
D000818:Animals; D001921:Brain; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000378:metabolism*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D046228:Microarray Analysis; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D010960:Plasminogen Activators / Q000235:genetics; D011480:Protease Inhibitors / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000235:genetics / Q000378:metabolism
D011480:Protease Inhibitors; D002403:Cathepsins; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D020169:Caspases; D020782:Matrix Metalloproteinases