Estrogen dissociates Tau and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit in postischemic hippocampus.
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.
Cardona-Gómez
Gloria Patricia
GP
Group of Neuroscience, School of Medicine, University of Antioquia, Cali, Colombia. patricia.cardona@neurociencias.udea.edu.co
Arango-Davila
Cesar
C
Gallego-Gómez
Juan Carlos
JC
Barrera-Ocampo
Alvaro
A
Pimienta
Hernan
H
Garcia-Segura
Luis Miguel
LM
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*
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