Prazosin, an alpha(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease
Por:
Katsouri, L, Vizcaychipi, MP, McArthur, S, Harrison, I, Suarez-Calvet, M, Lleo, A, Lloyd, DG, Ma, DQ, Sastre, M
Publicada:
1 abr 2013
Resumen:
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 alpha(1)-adrenoceptor antagonist, was able to reduce the generation of amyloid beta 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. (C) 2013 Elsevier Inc. All rights reserved.
Filiaciones:
Katsouri, L:
Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Brain Sci, London W12 0NN, England
Vizcaychipi, MP:
Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London W12 0NN, England
McArthur, S:
Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Brain Sci, London W12 0NN, England
Harrison, I:
Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Brain Sci, London W12 0NN, England
Suarez-Calvet, M:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
Lleo, A:
Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Dept Neurol, E-08193 Barcelona, Spain
CIBERNED, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Lloyd, DG:
Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London W12 0NN, England
Ma, DQ:
Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London W12 0NN, England
Sastre, M:
Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Brain Sci, London W12 0NN, England
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