We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Early administration of RS 67333, a specific 5-HT<sub>4</sub> receptor agonist, prevents amyloidogenesis and behavioral deficits in the 5XFAD mouse model of Alzheimer's disease.
- Authors
Giannoni, Patrizia; Gaven, Florence; de Bundel, Dimitri; Baranger, Kevin; Marchetti-Gauthier, Evelyne; Roman, François S.; Valjent, Emmanuel; Marin, Philippe; Bockaert, Joël; Rivera, Santiago; Claeysen, Sylvie
- Abstract
Amyloid β (Aβ) accumulation is considered the main culprit in the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that decreasing Aβ production at very early stages of AD could be a promising strategy to slow down disease progression. Serotonin 5-HT4 receptor activation stimulates α-cleavage of the amyloid precursor protein (APP), leading to the release of the soluble and neurotrophic sAPPα fragment and thus precluding Aβ formation. Using the 5×FAD mouse model of AD that shows accelerated Aβ deposition, we investigated the effect of chronic treatments (treatment onset at different ages and different durations) with the 5-HT4 receptor agonist RS 67333 during the asymptomatic phase of the disease. Chronic administration of RS 67333 decreased concomitantly the number of amyloid plaques and the level of Aβ species. Reduction of Aβ levels was accompanied by a striking decrease in hippocampal astrogliosis and microgliosis. RS 67333 also transiently increased sAPPα concentration in the cerebrospinal fluid and brain. Moreover, a specific 5-HT4 receptor antagonist (RS 39604) prevented the RS 67333-mediated reduction of the amyloid pathology. Finally, the novel object recognition test deficits of 5×FAD micewere reversed by chronic treatment with RS 67333. Collectively, these results strongly highlight this 5-HT4 receptor agonist as a promising disease modifying-agent for AD.
- Subjects
AMYLOID; CHEMICAL agonists; ALZHEIMER'S disease; GLIOSIS; LABORATORY mice
- Publication
Frontiers in Aging Neuroscience, 2013, Vol 5, p1
- ISSN
1663-4365
- Publication type
Article
- DOI
10.3389/fnagi.2013.00096