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Intranasal deferoxamine engages multiple pathways to decrease memory loss in the APP/PS1 model of amyloid accumulation.
- Source :
-
Neuroscience letters [Neurosci Lett] 2015 Jan 01; Vol. 584, pp. 362-7. Date of Electronic Publication: 2014 Nov 13. - Publication Year :
- 2015
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Abstract
- In addition to the hallmark accumulation of amyloid and hyper-phosphorylation of tau, brain changes in Alzheimer's disease are multifactorial including inflammation, oxidative stress, and metal dysregulation. Metal chelators have been explored as a less well known approach to treatment. One chelator currently being developed is deferoxamine (DFO), administered via the intranasal (IN) route. In the current study, APP/PS1 amyloid mice were treated with a chronic, low dose of IN DFO, subjected to a rigorous battery of behavior tests, and the mechanism of action was examined. Mice were treated 3x/week with 0.24 C IN DFO for 18 weeks from 36 to 54 weeks of age, 4 weeks of behavior tests were performed that included both working and reference memory, anxiolytic and motor behaviors, and finally brain tissues were analyzed for amyloid, protein oxidation, and other proteins affected by DFO. We found that IN DFO treatment significantly decreased loss of both reference and working memory in the Morris and radial arm water mazes (p < 0.05), and also decreased soluble Aβ40 and Aβ42 in cortex and hippocampus (p < 0.05). Further, IN DFO decreased activity of GSK3β, and led to decreases in oxidative stress (p < 0.05). These data demonstrate that low doses of IN DFO can modify several targets along the multiple pathways implicated in the neuropathology of Alzheimer's, making it an attractive candidate for the treatment of this heterogeneous disease.<br /> (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Administration, Intranasal
Alzheimer Disease metabolism
Alzheimer Disease psychology
Animals
Deferoxamine therapeutic use
Glycogen Synthase Kinase 3 metabolism
Glycogen Synthase Kinase 3 beta
Iron Chelating Agents therapeutic use
Male
Memory Disorders metabolism
Memory Disorders psychology
Memory, Long-Term drug effects
Memory, Short-Term drug effects
Mice, Transgenic
Oxidative Stress
Signal Transduction
beta Catenin
Alzheimer Disease drug therapy
Amyloid metabolism
Amyloid beta-Protein Precursor genetics
Deferoxamine pharmacology
Iron Chelating Agents pharmacology
Memory Disorders drug therapy
Presenilin-1 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1872-7972
- Volume :
- 584
- Database :
- MEDLINE
- Journal :
- Neuroscience letters
- Publication Type :
- Academic Journal
- Accession number :
- 25445365
- Full Text :
- https://doi.org/10.1016/j.neulet.2014.11.013