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Increased sensitivity to seizures in mice lacking cellular prion protein
R Walz1, O B Amaral, I C Rockenbach
1Centro de Memória, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. rogerwalz@hotmail.com
Epilepsia
|December 28, 1999
Summary
Mice lacking cellular prion protein (PrPc) show increased seizure susceptibility and mortality when exposed to convulsant agents. This highlights a potential role for PrPc in epilepsy, warranting further investigation in human conditions.
Area of Science:
- Neuroscience
- Prion Biology
- Epilepsy Research
Background:
- The physiological function of cellular prion protein (PrPc) remains largely unknown.
- Mice lacking PrPc exhibit normal development with only minor deficits, suggesting subtle roles.
Purpose of the Study:
- To investigate the potential role of PrPc in seizure threshold and epilepsy.
- To assess the sensitivity of PrPc knockout mice to various seizure-inducing agents.
Main Methods:
- PrPc knockout mice and wild-type controls were subjected to pentylenetetrazol (PTZ)-induced kindling and seizures.
- Seizure susceptibility was also evaluated using kainic acid and pilocarpine to induce status epilepticus (SE).
Main Results:
- PrPc knockout mice exhibited significantly accelerated seizure progression and higher mortality rates during PTZ kindling compared to wild-type controls.
- Knockout mice showed increased mortality and seizure severity after single PTZ injections, pilocarpine-induced SE, and kainic acid administration.
- Notably, 70% of knockout mice developed severe seizures after kainic acid, while no wild-type animals did.
Conclusions:
- The absence of cellular prion protein significantly increases susceptibility to seizures induced by diverse convulsant agents.
- This heightened seizure sensitivity represents a major phenotype in PrPc-null mice, contrasting with initial observations of normalcy.
- The findings suggest a potential role for PrPc in human epilepsies, including chronic, idiopathic, secondary, and cryptogenic forms, meriting further research.