title: Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus.
abstract: During cerebral ischemia, part of the damage associated with the hyperactivation of glutamate receptors results from the hyperphosphorylation of the microtubule-associated protein Tau. Previous studies have shown that estradiol treatment reduces neural damage after cerebral ischemia. Here, we show that transient occlusion of the middle cerebral artery results in the hyperphosphorylation of Tau and in a significant increase in the association of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid type glutamate receptor subunits 2/3 in the hippocampus. Estradiol treatment decreased hippocampal injury, inhibited glycogen synthase kinase-3beta and decreased the hyperphosphorylation of Tau and the interaction of Tau with glycogen synthase kinase-3beta and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor. These findings suggest that ischemia produces a strong association between Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor, and estradiol can exert at least part of its neuroprotective activity through inhibition of glycogen synthase kinase-3beta.
authors.affiliation: Group of Neuroscience, School of Medicine, University of Antioquia, Cali, Colombia. patricia.cardona@neurociencias.udea.edu.co
authors.forename: Gloria Patricia
authors.initials: GP
authors.lastname: Cardona-Gómez
authors.forename: Cesar
authors.initials: C
authors.lastname: Arango-Davila
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gallego-Gómez
authors.forename: Alvaro
authors.initials: A
authors.lastname: Barrera-Ocampo
authors.forename: Hernan
authors.initials: H
authors.lastname: Pimienta
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology*; D004958:Estradiol / Q000008:administration & dosage*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; D016875:tau Proteins; D004958:Estradiol; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3