title: Threshold for epileptiform activity is elevated in prion knockout mice.
abstract: Prion protein (PrP) is abundant in the nervous system, but its role remains uncertain. Prion diseases depend on an aggregation of the protein that is likely to interfere with its normal function. Loss of function does not in itself cause neurodegeneration, but whether it contributes to the clinical features of the disease remains an open question. Patients with classical Creutzfeldt-Jakob disease (CJD) have a higher than expected incidence of epilepsy. To study the mechanisms by which loss of PrP function may underlie changes in vulnerability to epilepsy in disease, we used several acute epilepsy models: we applied a variety of convulsant treatments (zero-magnesium, bicuculline, and pentylenetetrazol) to slices in vitro from PrP knockout (Prnp0/0) and control mice. In all three epilepsy models, we found that longer delays and/or higher concentrations of convulsants were necessary to generate spontaneous epileptiform activity in Prnp0/0 mice. These results together indicate an increased seizure threshold in Prnp0/0 mice, suggesting that loss of PrP function cannot explain a predisposition to seizures initiation in CJD.
authors.affiliation: Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. sratte@pitt.edu
authors.forename: S
authors.initials: S
authors.lastname: Ratté
authors.forename: M
authors.initials: M
authors.lastname: Vreugdenhil
authors.forename: J K R
authors.initials: JK
authors.lastname: Boult
authors.forename: A
authors.initials: A
authors.lastname: Patel
authors.forename: E A
authors.initials: EA
authors.lastname: Asante
authors.forename: J
authors.initials: J
authors.lastname: Collinge
authors.forename: J G R
authors.initials: JG
authors.lastname: Jefferys
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003292:Convulsants / Q000494:pharmacology; D007562:Creutzfeldt-Jakob Syndrome / Q000150:complications / Q000378:metabolism; D004195:Disease Models, Animal; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011328:Prions / Q000378:metabolism*
chemical_list: D003292:Convulsants; D011328:Prions