Dynamic Changes of Proteases and Protease Inhibitors Revealed by Microarray Analysis in CA3 and Entorhinal Cortex during Epileptogenesis in the Rat

• Published in: Epilepsia (Copenhagen) 2007-09, Vol.48 (s5), p.53-64
• Main Authors: Gorter, Jan A., Van Vliet, Erwin A., Rauwerda, Han, Breit, Timo, Stad, Robert, Van Schaik, Linda, Vreugdenhil, Erno, Redeker, Sandra, Hendriksen, Erik, Aronica, Eleonora, Da Silva, Fernando H. Lopes, Wadman, Wytse J.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Brain; Calpain; Caspases; Caspases - genetics; Caspases - metabolism; Cathepsins; Cathepsins - genetics; Cathepsins - metabolism; Disease Models, Animal; Electroconvulsive therapy; Entorhinal Cortex - metabolism; Epilepsy; Epilepsy, Temporal Lobe - genetics; Epilepsy, Temporal Lobe - metabolism; Gene Expression; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - metabolism; Investigative techniques, diagnostic techniques (general aspects); Male; Matrix metalloproteinases; Matrix Metalloproteinases - genetics; Matrix Metalloproteinases - metabolism; Medical sciences; Microarray Analysis; Nervous system; Nervous system (semeiology, syndromes); Neurology; Peptide Hydrolases - genetics; Peptide Hydrolases - metabolism; Plasminogen activator; Plasminogen Activators - genetics; Protease Inhibitors - metabolism; Protease Inhibitors - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Rats; Rats, Sprague-Dawley; Status epilepticus; Status Epilepticus - genetics; Status Epilepticus - metabolism; Treatments
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2007.01290.x

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.