journal.pone.0004590.PDF 460,86KB
1000 Titel
  • Improved Learning and Memory in Aged Mice Deficient in Amyloid β-Degrading Neutral Endopeptidase
1000 Autor/in
  1. Walther, Thomas |
  2. Albrecht, Doris |
  3. Becker, Matthias |
  4. Schubert, Manja |
  5. Kouznetsova, Elena |
  6. Wiesner, Burkard |
  7. Maul, Björn |
  8. Schliebs, Reinhard |
  9. Grecksch, Gisela |
  10. Furkert, Jens |
  11. Sterner-Kock, Anja |
  12. Schultheiss, Heinz-Peter |
  13. Becker, Axel |
  14. Siems, Wolf-Eberhard |
1000 Erscheinungsjahr 2009
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2009-02-25
1000 Erschienen in
1000 Quellenangabe
  • 4(2): e4590
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2009
1000 Lizenz
1000 Verlagsversion
  • |
  • |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • BACKGROUND: Neutral endopeptidase, also known as neprilysin and abbreviated NEP, is considered to be one of the key enzymes in initial human amyloid-β (Aβ) degradation. The aim of our study was to explore the impact of NEP deficiency on the initial development of dementia-like symptoms in mice. METHODOLOGY/PRINCIPAL FINDINGS: We found that while endogenous Aβ concentrations were elevated in the brains of NEP-knockout mice at all investigated age groups, immunohistochemical analysis using monoclonal antibodies did not detect any Aβ deposits even in old NEP knockout mice. Surprisingly, tests of learning and memory revealed that the ability to learn was not reduced in old NEP-deficient mice but instead had significantly improved, and sustained learning and memory in the aged mice was congruent with improved long-term potentiation (LTP) in brain slices of the hippocampus and lateral amygdala. Our data suggests a beneficial effect of pharmacological inhibition of cerebral NEP on learning and memory in mice due to the accumulation of peptides other than Aβ degradable by NEP. By conducting degradation studies and peptide measurements in the brain of both genotypes, we identified two neuropeptide candidates, glucagon-like peptide 1 and galanin, as first potential candidates to be involved in the improved learning in aged NEP-deficient mice. CONCLUSIONS/SIGNIFICANCE: Thus, the existence of peptides targeted by NEP that improve learning and memory in older individuals may represent a promising avenue for the treatment of neurodegenerative diseases.
1000 Sacherschließung
lokal Learning
lokal Learning and memory
lokal Peptides
lokal Animal behavior
lokal Mouse models
lokal Mice
lokal Hippocampus
lokal Human learning
1000 Fachgruppe
  1. Biologie |
1000 Fächerklassifikation (DDC)
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