Rapid Communication Increased Sensitivity to Seizures in Mice Lacking Cellular Prion Protein

Summary: Purpose: The physiologic role of the cellular prion protein (PrP') is unknown. Mice devoid of PrPC develop nor- mally and show only minor deficits. However, electrophysi- ologic and histologic alterations found in these mice suggest a possible role for PrP" in seizure threshold andor epilepsy. Methods: We tested the sensitivity of PrP" knockout mice to seizures induced by single convulsant or repeated subconvul- sant (kindling) doses of pentylenetetrazol (PTZ), and to status epilepticus (SE) induced by kainic acid or pilocarpine. Results: In PTZ kindling, seizure severity progressed faster in the PrP' knockout group, in which 92.8% reached stage 5 or death after 4 days of stimulation, as opposed to 38.4% in wild- type animals. After 10 injections, mortality was 85.7% among knockouts and 15.3% among controls. After a single PTZ in- jection (60 mgkg), overall mortality due to seizures was 91 % in knockout mice, but only 33% among wild-type animals. Pilocarpine-induced SE (320 mgkg) caused an 86.7% mortal- ity in knockouts, as opposed to 40% in wild-type animals. Finally, after kainic acid injections (10 mgkg), 70% of the knockouts developed at least one severe seizure, and 50% showed repetitive seizures, whereas

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