title: Chemical hypoxia facilitates alternative splicing of EAAT2 in presymptomatic APP23 transgenic mice.
abstract: Hypoxia is one of the major common components of vascular risk factors for pathogenesis of Alzheimer's disease. This study investigated the possible relationship between hypoxia and alternative splicing of the excitatory amino acid transporter 2 (EAAT2) in a transgenic model for Alzheimer's disease. We used an APP23 mouse model prior to amyloid deposition and subjected it to chemical hypoxia treatment as induced by 3-nitropropionic acid. One hour after administration of 3-nitropropionic acid changes in the expression of the 5'-splice forms mEAAT2/5UT3, mEAAT2/5UT4, and mEAAT2/5UT5 were found in the frontal cortex, hippocampus and cerebellum of the APP23 model. In untreated APP23 animals the expression of EAAT2 splice variants was unchanged. Our results demonstrate that hypoxia facilitates alternative splicing of EAAT2 in the APP23 model. This may be a molecular mechanism linking vascular factors to early pathophysiology of Alzheimer's disease.
authors.affiliation: Department of Neurology, Jewish Hospital Berlin, Heinz-Galinski-Str. 1, 13347 Berlin, Germany. christoph.muench@uni-ulm.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Münch
authors.forename: Bing-gen
authors.initials: BG
authors.lastname: Zhu
authors.forename: Andreas
authors.initials: A
authors.lastname: Mink
authors.forename: Ulrich
authors.initials: U
authors.lastname: Seefried
authors.forename: Matthias W
authors.initials: MW
authors.lastname: Riepe
authors.forename: Albert C
authors.initials: AC
authors.lastname: Ludolph
authors.forename: Thomas
authors.initials: T
authors.lastname: Meyer
mesh_terms: D017398:Alternative Splicing; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016564:Amyloid beta-Protein Precursor; D027342:Excitatory Amino Acid Transporter 2; C493396:Slc1a2 protein, mouse