Katarzyna Lukasiuk1, Terhi J Pirttilä, Asla Pitkänen. 1. 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
Abstract
PURPOSE: 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.
PURPOSE: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.
Authors: Jill L Wegrzyn; Steven J Bark; Lydiane Funkelstein; Charles Mosier; Angel Yap; Parsa Kazemi-Esfarjani; Albert R La Spada; Christina Sigurdson; Daniel T O'Connor; Vivian Hook Journal: J Proteome Res Date: 2010-10-01 Impact factor: 4.466
Authors: Daniel C Lee; Ceceile W Mason; Carl B Goodman; Maurice S Holder; Otis W Kirksey; Tracy A Womble; Walter B Severs; Donald E Palm Journal: Neurochem Res Date: 2007-04-18 Impact factor: 3.996
Authors: Gurjinder Kaur; Panaiyur Mohan; Monika Pawlik; Steven DeRosa; Jay Fajiculay; Shaoli Che; Anders Grubb; Stephen D Ginsberg; Ralph A Nixon; Efrat Levy Journal: Am J Pathol Date: 2010-10-01 Impact factor: 4.307
Authors: Eillen J Rodriguez-Franco; Yisel M Cantres-Rosario; Marines Plaud-Valentin; Rafael Romeu; Yolanda Rodríguez; Richard Skolasky; Viviana Meléndez; Carmen L Cadilla; Loyda M Melendez Journal: PLoS One Date: 2012-05-31 Impact factor: 3.240