Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease

Katsouri, L., Vizcaychipi, M.P., McArthur, S., Harrison, I., Suárez-Calvet, M., Lleo, A., Lloyd, D.G., Ma, D. and Sastre, M. 2013. Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease. Neurobiology of Aging. 34 (4), pp. 1105-15.

TitlePrazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease
AuthorsKatsouri, L., Vizcaychipi, M.P., McArthur, S., Harrison, I., Suárez-Calvet, M., Lleo, A., Lloyd, D.G., Ma, D. and Sastre, M.
Abstract

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.

JournalNeurobiology of Aging
Journal citation34 (4), pp. 1105-15
ISSN1558-1497
YearApr 2013
PublisherElsevier
Digital Object Identifier (DOI)doi:10.1016/j.neurobiolaging.2012.09.010
Publication dates
PublishedApr 2013

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