Increased sensitivity to seizures in mice lacking cellular prion protein

Increased sensitivity to seizures in mice lacking cellular prion protein

Author Walz, Roger Google Scholar
Amaral, Olavo B. Google Scholar
Rockenbach, Isabel C. Google Scholar
Roesler, Rafael Google Scholar
Izquierdo, Ivan Google Scholar
Cavalheiro, Esper Abrão Autor UNIFESP Google Scholar
Martins, Vilma R. Google Scholar
Brentani, Ricardo R. Google Scholar
Institution Univ Fed Rio Grande Sul
Universidade Federal de São Paulo (UNIFESP)
Ludwig Inst Canc Res
Abstract Purpose: the physiologic role of the cellular prion protein (PrPc) is unknown. Mice devoid of PrPc develop normally and show only minor deficits. However, electrophysiologic and histologic alterations found in these mice suggest a possible:role fur PrPc in seizure threshold and/or epilepsy.Methods: We tested the sensitivity of PrPc knockout mice to seizures induced by single convulsant or repeated subconvulsant (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 PrPc knockout group, in which 92.8% reached stage 5 or death after 4 days of stimulation, as opposed to 38.4% in wildtype animals: After 10 injections, mortality was 85.7% among knockouts and 15.3% among controls. After a single PTZ injection (60 mg/kg), overall mortality due to seizures was 91% in knockout mice, but only 33% among wild-type animals. Pilocarpine-induced SE (320 mg/kg) caused an 86.7% mortality in knockouts, as opposed to 40% in wild-type animals. Finally, after kainic acid injections (10 mg/kg), 70% of the knockouts developed at least one severe seizure, and 50% showed repetitive seizures, whereas no wild-type animal exhibited observable seizures.Conclusions: Animals lacking cellular prion protein expression are more susceptible to seizures induced by various convulsant agents. This is perhaps the most striking alteration yet found in PrPc-null mice, who at first analysis appeared to be completely normal. A possible role for PrPc in chronic and idiopathic (familial), secondary, or cryptogenic epilepsies in humans remains to be investigated.
Keywords prion
Language English
Date 1999-12-01
Published in Epilepsia. Philadelphia: Lippincott Williams & Wilkins, v. 40, n. 12, p. 1679-1682, 1999.
ISSN 0013-9580 (Sherpa/Romeo, impact factor)
Publisher Lippincott Williams & Wilkins
Extent 1679-1682
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000084175200001

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