Lack of Neprilysin Suffices to Generate Murine Amyloid-like Deposits in the Brain and Behavioral Deficit in Vivo.
From: Institute of Anatomy, University of Zurich, Zurich, Switzerland.
Journal of neuroscience research
- Publish Date: Dec 2006
- ISSN: 0360-4012
- Volume: 84
- Issue: 8
- Pages: 1871-8
- Medium: Print
- Language: English
- Citation (JAMA): Madani Rime, Poirier Raphael, Wolfer David P, et al. Lack of Neprilysin Suffices to Generate Murine Amyloid-like Deposits in the Brain and Behavioral Deficit in Vivo.. J. Neurosci. Res. Dec 2006;84:1871-8
Abstract
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.
Mesh Headings (Keywords): Age Factors, Amyloid, Analysis of Variance, Animals, Avoidance Learning, Behavior, Animal, Brain, Conditioning, Operant, Enzyme-Linked Immunosorbent Assay, Maze Learning, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Transmission, Neprilysin, Water Deprivation
Check for Full Text / PubMed Unique Identifier (PMID): 16998901
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