Upregulation of cystatin C expression in the rat hippocampus during epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy.
OBJECTIVE
Cystatin C is a cysteine proteinase inhibitor with widespread distribution in body fluids and tissues, abundant in the cerebrospinal fluid and in brain tissue. There is an implied role for cystatin C in several neurologic disorders, but the actual function of cystatin C in the brain remains unknown. Moreover, the reports on the distribution of cystatin C in the brain are controversial. We present the data on the distribution of cystatin C in normal brain tissue and during epileptogenesis.


METHODS
Epileptogenesis was triggered by inducing self-sustained status epilepticus (SSSE) with a 20- to 30-min electrical stimulation of the amygdala in rats. Animals were monitored continuously for 2 weeks with video-EEG to ascertain that they were in an epileptogenic phase.


RESULTS
Analysis of double-stained immunopreparations indicated that in normal brain, cystatin C is expressed mainly in microglia. In epileptogenic animals, immunostaining was increased in the microglia as well as in the neuropil at 4 days, 1 week, and 2 weeks after SSSE. Moreover, the density of cystatin C-positive microglia was associated with the severity of neuronal damage in the CA1 subfield of the hippocampus.


CONCLUSIONS
This is the first report linking cystatin C with epileptogenesis and epilepsy. Further studies will explore the potential neuroprotective functions of this protein during epileptogenesis and whether the manipulation of its expression or function will have therapeutic implications.
Lukasiuk
Katarzyna
K
Epilepsy Research Laboratory, A.I. Virtanen Institute for Molecular Sciences, University of Kuopio, PO Box 1627, FIN-70 211 Kuopio, Finland. Katarzyna.Lukasiuk@uku.fi
Pirttilä
Terhi J
TJ
Pitkänen
Asla
A
D000679:Amygdala; D000818:Animals; D055316:Cystatin C; D015891:Cystatins / Q000378:metabolism*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D013997:Time Factors; D014018:Tissue Distribution; D015854:Up-Regulation
C525032:Cst3 protein, rat; D055316:Cystatin C; D015891:Cystatins