title: Cell type-specific action of seizure-induced intracellular zinc accumulation in the rat hippocampus.
abstract: Increased levels of intracellular zinc have been implicated in neuronal cell death in ischaemia, epilepsy and traumatic brain damage. However, decreases in zinc levels also lead to increased neuronal death and lowered seizure threshold. In the present study we investigated the physiological role of zinc in neurodegeneration and protection following epileptic seizures. Cells located in the strata oriens and lucidum of the CA3 region accumulated high concentrations of zinc and died. A decrease in zinc level could prevent the death of these neurones after seizures. Most of these cells were GABAergic interneurones. In contrast, neurones in the CA3 pyramidal cell layer accumulated moderate amounts of zinc and survived. Zinc chelation led to an increase in the mortality rate of these cells. Furthermore, in these cells low concentrations of intracellular zinc activated Akt (protein kinase B), thus providing protection against neurodegeneration. These results demonstrate that intracellularly accumulated zinc can be neurotoxic or neuroprotective depending on its concentration. This dual action is cell type specific.
authors.affiliation: Centre de recherche Université Laval Robert Giffard, 2601 chemin de la Canardière, Québec, QC, G1J 2G3 Canada.
authors.forename: Amélie
authors.initials: A
authors.lastname: Côté
authors.forename: Marilou
authors.initials: M
authors.lastname: Chiasson
authors.forename: Modesto R
authors.initials: MR
authors.lastname: Peralta
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lafortune
authors.forename: Luca
authors.initials: L
authors.lastname: Pellegrini
authors.forename: Katalin
authors.initials: K
authors.lastname: Tóth
mesh_terms: D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D014018:Tissue Distribution; D015032:Zinc / Q000378:metabolism*
chemical_list: D015032:Zinc