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

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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.

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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

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Acknowledgment

This work was supported by a grant from the VERUM foundation.

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Authors and Affiliations

  1. Department of Neurology, Jewish Hospital Berlin, Heinz-Galinski-Str. 1, 13347, Berlin, Germany

    Christoph Münch

  2. Department of Neurology, University of Ulm, Steinhövelstr. 1, 89075, Ulm, Germany

    Christoph Münch, Bing-gen Zhu, Andreas Mink, Ulrich Seefried, Matthias W. Riepe & Albert C. Ludolph

  3. Department of Neurology, Charité Hospital, Humboldt University, 13353, Berlin, Germany

    Thomas Meyer

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  1. Christoph Münch
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  2. Bing-gen Zhu
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  3. Andreas Mink
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Correspondence to Christoph Münch.

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Münch, C., Zhu, Bg., Mink, A. et al. Chemical Hypoxia Facilitates Alternative Splicing of EAAT2 in Presymptomatic APP23 Transgenic Mice. Neurochem Res 33, 1005–1010 (2008). https://doi.org/10.1007/s11064-007-9540-5

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  • DOI: https://doi.org/10.1007/s11064-007-9540-5

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