NR ATIC
AU de Cabo,C.; Prieto-Martin,A.; Laffont-Proust,I.; Hässig,R.; Aceves Luquero,C.I.; Sanchez-Prieto,R.; Munoz de la Pascua,L.; Lopez,D.E.; Volland,H.; Moya,K.L.
TI Brain PrPc is increased during audiogenic seizures.
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-34
PT Konferenz-Poster
AB
Prion diseases such as Creutzfeldt-Jakob disease (CJD) are characterized by accumulation of PrPsc, a protease resistant conformer of the cellular prion protein (PrPc) heavily expressed in neurons. Abnormal EEG activity or epileptiform discharges have been reported in a number of sporadic and familial cases of CJD. These observations coupled with an increased sensitivity to seizures in some PrP null mice and the association of a Prnp polymorphism with a mesial temporal epilepsy suggest a relationship between PrPc and neuronal activity. Here we examined changes in PrPc after inducing massive neuronal discharge in a genetic model of epileptic susceptibility. Control and inbred, susceptible to audiogenic seizures (GASH:Sal) hamsters were stimulated (white noise: 1-37 KHz, 30-80 db, 10 sec) twice a day for five days, while non-stimulated hamsters served as controls. None of the stimulated control hamsters showed seizures, while the stimulation produced generalized seizures lasting about 30 sec in all of the GASH:Sal hamsters. We used the two-site immunometric assay to evaluate PrPc levels in homogenates of the inferior colliculus (IC), cortex (CTX) and hippocampus (HIP) and the brainstem (BST). One-way ANOVA showed a significant effect for PrPc levels in the IC (p< 0.02) but no significant effects in the CTX, HIP or BST. Posthoc analysis showed a significant increase in PrPc in the stimulated GASH:Sal compared to the other groups (p<0.02).
We analyzed the same IC homogenates the ubiquitous synaptic vesicle protein 2 (SV2) and GAP-43, a marker for early neuronal reorganization. Western blot analysis showed no significant differences in SV2. GAP-43 was significantly increased in stimulated GASH:Sal animals compared with non-stimulated animals (p<0.02). Our results show that epileptic discharge increases local levels of PrPc. These results suggest that PrPc may be linked to synaptic reorganization associated with changes in neuronal activity. Support:FIS01/3018,GISPrion
AD Carlos de Cabo, Ana Prieto-Martín, Complejo Hospitalario Universitario de Albacete-SESCAM, Spain; Isabelle Laffont-Proust, INSERM Avenir team "Human prion diseases",Salpêtrière Hospital, Paris, France; Raymonde Hässig, CEA-CNRS URA 2210, Service Hospitalier Frédéric Joliot, Orsay cedex, France; Clara Isabel Aceves Luquero, Ricardo Sánchez-Prieto, CRIB - Universidad de Castilla-La Mancha, Albacete, Spain; Luis Muñoz de la Pascua, Dolores E. López, INCYL - Universidad de Salamanca, Spain; Hervé Volland, CEA, Service de Pharmacologie et d'Immunologie, Gif-sur-Yvette cedex, France; Kenneth L. Moya, CNRS UMR 8542; Ecole Normal Superièure, Paris, France
SP englisch
PO Deutschland