Cystatin C, a cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy.
Cystatin C (CSTC), a cysteine protease inhibitor, has been implicated in the processes of neuronal degeneration and repair of the nervous system. Using serial analysis of gene expression (SAGE), we recently identified CSTC as one of the genes that are overexpressed after electrically induced status epilepticus (SE). In the present study, Western blot analysis extended the SAGE results, showing increased CSTC protein in the hippocampus and entorhinal cortex. Immunocytochemistry revealed an increase in CSTC expression in glial cells, which was first apparent 24 h after onset of SE, and persisted for at least 3 months. Double immunolabelling confirmed that both reactive astrocytes, and activated microglia were CSTC immunopositive. Within the hippocampus, up-regulation was also observed in neuronal cells within one day after SE. Up-regulation was still present in hippocampal pyramidal cells and surviving interneurons of chronic epileptic rats (3-8 months post-SE). This study demonstrates that status epilepticus leads to a widespread and persistent up-regulation of CSTC in the hippocampus and entorhinal cortex, which may represent an intrinsic neuroprotective mechanism in the course of epileptogenesis that may counteract progression of the disease.
Aronica
E
E
Department of (Neuro)-Pathology, Academic Medical Centre, University of Amsterdam, The Netherlands.
van Vliet
E A
EA
Hendriksen
E
E
Troost
D
D
Lopes da Silva
F H
FH
Gorter
J A
JA
D000818:Animals; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D030161:Avian Proteins; D051926:Basigin; D001798:Blood Proteins; D015153:Blotting, Western; D064026:Calbindins; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010320:Parvalbumins / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D014746:Vimentin / Q000378:metabolism
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D030161:Avian Proteins; D001798:Blood Proteins; C102624:Bsg protein, Gallus gallus; C079432:Bsg protein, rat; D064026:Calbindins; C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D005904:Glial Fibrillary Acidic Protein; D008562:Membrane Glycoproteins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D014746:Vimentin; D051926:Basigin; D003546:Cysteine Endopeptidases