In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 28, No. 45 ( 2008-11-05), p. 11622-11634
Abstract:
Recent studies have revealed that disruption of vitamin A signaling observed in Alzheimer's disease (AD) leads to β-amyloid (Aβ) accumulation and memory deficits in rodents. The aim of the present study was to evaluate the therapeutic effect of all- trans retinoic acid (ATRA), an active metabolite of vitamin A, on the neuropathology and deficits of spatial learning and memory in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic mice, a well established AD mouse model. Here we report a robust decrease in brain Aβ deposition and tau phosphorylation in the blinded study of APP/PS1 transgenic mice treated intraperitoneally for 8 weeks with ATRA (20 mg/kg, three times weekly, initiated when the mice were 5 months old). This was accompanied by a significant decrease in the APP phosphorylation and processing. The activity of cyclin-dependent kinase 5, a major kinase involved in both APP and tau phosphorylation, was markedly downregulated by ATRA treatment. The ATRA-treated APP/PS1 mice showed decreased activation of microglia and astrocytes, attenuated neuronal degeneration, and improved spatial learning and memory compared with the vehicle-treated APP/PS1 mice. These results support ATRA as an effective therapeutic agent for the prevention and treatment of AD.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.3153-08.2008
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2008
detail.hit.zdb_id:
1475274-8
SSG:
12
Permalink
