Neurochemical Research

, Volume 33, Issue 6, pp 1005–1010

Chemical Hypoxia Facilitates Alternative Splicing of EAAT2 in Presymptomatic APP23 Transgenic Mice

  • Christoph Münch
  • Bing-gen Zhu
  • Andreas Mink
  • Ulrich Seefried
  • Matthias W. Riepe
  • Albert C. Ludolph
  • Thomas Meyer
Original Paper

DOI: 10.1007/s11064-007-9540-5

Cite this article as:
Münch, C., Zhu, B., Mink, A. et al. Neurochem Res (2008) 33: 1005. doi:10.1007/s11064-007-9540-5

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.

Keywords

Alzheimer’s diseaseHypoxiaExcitatory amino acid transporter 2Alternative splicing3-Nitropropionic acidMouse model

Abbreviations

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

ANOVA

Analysis of variance

APP

Amyloid precursor protein

EAAT2

Excitatory amino acid transporter 2

3-NP

3-Nitropropionic acid

uORF

Upstream open reading frame

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Christoph Münch
    • 1
    • 2
  • Bing-gen Zhu
    • 2
  • Andreas Mink
    • 2
  • Ulrich Seefried
    • 2
  • Matthias W. Riepe
    • 2
  • Albert C. Ludolph
    • 2
  • Thomas Meyer
    • 3
  1. 1.Department of NeurologyJewish Hospital BerlinBerlinGermany
  2. 2.Department of NeurologyUniversity of UlmUlmGermany
  3. 3.Department of NeurologyCharité Hospital, Humboldt UniversityBerlinGermany