Cystatin C modulates neurodegeneration and neurogenesis following status epilepticus in mouse.
Brain damaging insults cause alterations in neuronal networks that trigger epileptogenesis, and eventually lead to the appearance of spontaneous seizures. The present experiments were designed to study the cellular expression and functions of a cysteine proteinase inhibitor, cystatin C, whose gene expression is previously shown to be upregulated in the rat hippocampus during status epilepticus (SE)-induced epileptogenesis. The present data showed that the expression of cystatin C protein increased in the mouse hippocampus 7 days following SE and localized mainly to astrocytes and microglia. Acute neuronal death in the hippocampus at 24 h after SE was reduced in cystatin C-/- mice. Also, the basal level of neurogenesis in the subgranular layer of dentate gyrus was decreased in cystatin C-/- mice compared to wildtype littermates. Interestingly, migration of newly born neurons within the granule cell layer was attenuated in cystatin C-/- mice. These data demonstrate that cystatin C has a role in neuronal death and neurogenesis during SE-induced network reorganization.
Pirttilä
Terhi J
TJ
A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, PO Box 1627, FIN-70211 Kuopio, Finland.
Lukasiuk
Katarzyna
K
Håkansson
Katarina
K
Grubb
Anders
A
Abrahamson
Magnus
M
Pitkänen
Asla
A
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D055316:Cystatin C; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009415:Nerve Net / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D013226:Status Epilepticus / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D013234:Stem Cells / Q000378:metabolism*
C525031:Cst3 protein, mouse; C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins; D018690:Excitatory Amino Acid Agonists