Prazosin, an α(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease.
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.
Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
Loukia
L
Katsouri
Marcela P
MP
Vizcaychipi
Simon
S
McArthur
Ian
I
Harrison
Marc
M
Suárez-Calvet
Alberto
A
Lleo
Dafydd G
DG
Lloyd
Daqing
D
Ma
Magdalena
M
Sastre
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011224:Prazosin / Q000627:therapeutic use*; D016896:Treatment Outcome
D058668:Adrenergic alpha-1 Receptor Antagonists; D016229:Amyloid beta-Peptides; D011224:Prazosin