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Aβ42 oligomers impair the bioenergetic activity in hippocampal synaptosomes derived from APP-KO mice

  • Benedikt Beckert , Amparo Acker-Palmer and Walter Volknandt EMAIL logo
Published/Copyright: January 9, 2018
Biological Chemistry
From the journal Biological Chemistry Volume 399 Issue 5

Abstract

Employing hippocampal synaptosomes from amyloid precursor protein (APP)-deleted mice we analyzed the immediate effects of amyloid beta peptide 42 (Aβ42) peptide in its oligomeric or fibrillar assembly or of soluble amyloid precursor protein alpha (sAPPα) protein on their bioenergetic activity. Upon administration of oligomeric Aβ42 peptide for 30 min we observed a robust decrease both in mitochondrial activity and in mitochondrial membrane potential (MMP). In contrast the respective fibrillary or scrambled peptides showed no effect, indicating that inhibition strictly depends on the oligomerization status of the peptide. Hippocampal synaptosomes from old APP-KO mice revealed a further reduction of their already impaired bioenergetic activity upon incubation with 10 μm Aβ42 peptide. In addition we evaluated the influence of the sAPPα protein on mitochondrial activity of hippocampal synaptosomes derived from young or old APP-KO animals. In neither case 20 nm nor 200 nm sAPPα protein had an effect on mitochondrial metabolic activity. Our findings demonstrate that hippocampal synaptosomes derived from APP-KO mice are a most suitable model system to evaluate the impact of Aβ42 peptide on its bioenergetic activity and to further elucidate the molecular mechanisms underlying the impairments by oligomeric Aβ42 on mitochondrial function. Our data demonstrate that extracellular Aβ42 peptide is taken up into synaptosomes where it immediately attenuates mitochondrial activity.

Keywords: amyloid-β; amyloid precursor protein; bioenergetic activity; hippocampal synaptosomes; mitochondrial membrane potential

Acknowledgments

We are grateful to Herbert Zimmermann for valuable suggestions. We thank Ulrike Müller for providing the animals. The authors declare that they have no conflicts of interest with the contents of this article. All experiments were conducted in compliance with the ARRIVE guidelines and according to the ethical guidelines of the Goethe University. This work was supported by grants from the Deutsche Forschungsgemeinschaft, Funder Id: 10.13039/501100001659, (SFB 834, SFB1080, FOR2325, EXC 115 and EXC 147), the Max Planck Fellow Program and Gutenberg Research College (GRC) at Johannes Gutenberg University Mainz (A. A.-P.).

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Received: 2017-09-08
Accepted: 2017-12-20
Published Online: 2018-01-09
Published in Print: 2018-04-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

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  1. Frontmatter
  2. Reviews
  3. Generation of superoxide and hydrogen peroxide by side reactions of mitochondrial 2-oxoacid dehydrogenase complexes in isolation and in cells
  4. Update on mitochondria and muscle aging: all wrong roads lead to sarcopenia
  5. Research Articles/Short Communications
  6. Protein Structure and Function
  7. CRISPR/Cas9-mediated modification of the extreme C-terminus impairs PDGF-stimulated activity of Duox2
  8. Membranes, Lipids, Glycobiology
  9. Changes of the peripheral blood mononuclear cells membrane fluidity from type 1 Gaucher disease patients: an electron paramagnetic resonance study
  10. Molecular Medicine
  11. Aβ42 oligomers impair the bioenergetic activity in hippocampal synaptosomes derived from APP-KO mice
  12. Cell Biology and Signaling
  13. Molecular determinants of Drosophila immunophilin FKBP39 nuclear localization
  14. The effect of lncRNA HOTAIR on chemoresistance of ovarian cancer through regulation of HOXA7
  15. Novel Techniques
  16. Determination of selenium during pathogenesis of hepatic fibrosis employing hydride generation and inductively coupled plasma mass spectrometry
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