Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo
| Autor: | Raphael Poirier, Rime Madani, Mohammed El Mouedden, Hans-Peter Lipp, Peter Groscurth, Hans Welzl, Bao Lu, Marc Mercken, Roger M. Nitsch, M. Hasan Mohajeri, David P. Wolfer |
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| Přispěvatelé: | University of Zurich, Mohajeri, M H |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Amyloid
2804 Cellular and Molecular Neuroscience Enzyme-Linked Immunosorbent Assay 610 Medicine & health Mice Cellular and Molecular Neuroscience Microscopy Electron Transmission In vivo mental disorders Avoidance Learning Amyloid precursor protein medicine Animals Maze Learning Neprilysin Pathological Mice Knockout Analysis of Variance Behavior Animal Water Deprivation biology fungi Neurodegeneration Age Factors Brain 11359 Institute for Regenerative Medicine (IREM) medicine.disease Pathophysiology Mice Inbred C57BL Taste aversion biology.protein Conditioning Operant Neuroscience |
| Popis: | Accumulation of the beta-amyloid peptide (Abeta) in the brain is a major pathological hallmark of Alzheimer's disease (AD), leading to synaptic dysfunction, neuronal death, and memory impairment. The levels of neprilysin, a major Abeta-degrading enzyme, are decreased in AD brains and during aging. Because neprilysin cleaves Abeta in vivo, its down-regulation may contribute to the pathophysiology of AD. The aim of this study was to assess the consequences of neprilysin deficiency on accumulation of murine Abeta in brains and associated pathologies in vivo by investigating neprilysin-deficient mice on biochemical, morphological, and behavioral levels. Aged neprilysin-deficient mice expressed physiological amyloid precursor protein (APP) levels and exhibited elevated brain Abeta concentrations and amyloid-like deposits in addition to signs of neuronal degeneration in their brains. Behaviorally, neprilysin-deficient mice acquired a significantly weaker conditioned taste aversion that extinguished faster than the aversion of age-matched controls. Our data establish that, under physiological APP expression levels, neprilysin deficiency is associated with increased Abeta accumulation in the brain and leads to deposition of amyloid-like structures in vivo as well as with signs of AD-like pathology and with behavioral deficits. |
| Databáze: | OpenAIRE |
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