PMID- 17999180 OWN - NLM STAT- MEDLINE DCOM- 20080724 LR - 20211020 IS - 0364-3190 (Print) IS - 0364-3190 (Linking) VI - 33 IP - 6 DP - 2008 Jun TI - Chemical hypoxia facilitates alternative splicing of EAAT2 in presymptomatic APP23 transgenic mice. PG - 1005-10 AB - 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. FAU - Munch, Christoph AU - Munch C AD - Department of Neurology, Jewish Hospital Berlin, Heinz-Galinski-Str. 1, 13347 Berlin, Germany. christoph.muench@uni-ulm.de FAU - Zhu, Bing-gen AU - Zhu BG FAU - Mink, Andreas AU - Mink A FAU - Seefried, Ulrich AU - Seefried U FAU - Riepe, Matthias W AU - Riepe MW FAU - Ludolph, Albert C AU - Ludolph AC FAU - Meyer, Thomas AU - Meyer T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071113 PL - United States TA - Neurochem Res JT - Neurochemical research JID - 7613461 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (Slc1a2 protein, mouse) SB - IM MH - *Alternative Splicing MH - Amyloid beta-Protein Precursor/genetics/*metabolism MH - Animals MH - Brain/metabolism MH - Excitatory Amino Acid Transporter 2/*genetics/metabolism MH - Humans MH - Hypoxia, Brain/chemically induced/*genetics/metabolism MH - Male MH - Mice MH - Mice, Transgenic EDAT- 2007/11/14 09:00 MHDA- 2008/07/25 09:00 CRDT- 2007/11/14 09:00 PHST- 2007/08/14 00:00 [received] PHST- 2007/10/30 00:00 [accepted] PHST- 2007/11/14 09:00 [pubmed] PHST- 2008/07/25 09:00 [medline] PHST- 2007/11/14 09:00 [entrez] AID - 10.1007/s11064-007-9540-5 [doi] PST - ppublish SO - Neurochem Res. 2008 Jun;33(6):1005-10. doi: 10.1007/s11064-007-9540-5. Epub 2007 Nov 13.