| First Author | Giannoni P | Year | 2013 |
| Journal | Front Aging Neurosci | Volume | 5 |
| Pages | 96 | PubMed ID | 24399967 |
| Mgi Jnum | J:311595 | Mgi Id | MGI:6771870 |
| Doi | 10.3389/fnagi.2013.00096 | Citation | Giannoni P, et al. (2013) Early administration of RS 67333, a specific 5-HT4 receptor agonist, prevents amyloidogenesis and behavioral deficits in the 5XFAD mouse model of Alzheimer's disease. Front Aging Neurosci 5:96 |
| abstractText | Amyloid beta (Abeta) accumulation is considered the main culprit in the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that decreasing Abeta production at very early stages of AD could be a promising strategy to slow down disease progression. Serotonin 5-HT4 receptor activation stimulates alpha-cleavage of the amyloid precursor protein (APP), leading to the release of the soluble and neurotrophic sAPPalpha fragment and thus precluding Abeta formation. Using the 5XFAD mouse model of AD that shows accelerated Abeta 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 Abeta species. Reduction of Abeta levels was accompanied by a striking decrease in hippocampal astrogliosis and microgliosis. RS 67333 also transiently increased sAPPalpha 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 5XFAD mice were 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. |
