Document Detail


Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease.
MedLine Citation:
PMID:  23063647     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Noradrenergic deficits have been described in the hippocampus and the frontal cortex of Alzheimer's disease brains, which are secondary to locus coeruleus degeneration. Locus coeruleus is the brain stem nucleus responsible for synthesis of noradrenaline and from where all noradrenergic neurons project. In addition, it has been suggested that noradrenaline might play a role in modulating inflammatory responses in Alzheimer's disease. In this study we aimed to investigate the effect of various agonists and antagonists for adrenergic receptors on amyloid precursor protein processing. Among them, we found that prazosin, an α(1)-adrenoceptor antagonist, was able to reduce the generation of amyloid β in N2a cells. Treatment of transgenic APP23 mice with prazosin prevented memory deficits over time. Although prazosin did not influence amyloid plaque load, it induced astrocytic proliferation and increased the release of apolipoprotein E and anti-inflammatory cytokines. These findings suggest that chronic treatment with prazosin leads to an anti-inflammatory response with potential beneficial effects on cognitive performance.
Authors:
Loukia Katsouri; Marcela P Vizcaychipi; Simon McArthur; Ian Harrison; Marc Suárez-Calvet; Alberto Lleo; Dafydd G Lloyd; Daqing Ma; Magdalena Sastre
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-11
Journal Detail:
Title:  Neurobiology of aging     Volume:  -     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
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