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- W2083863921 abstract "While polyphenolic compounds have many health benefits, the potential development of polyphenols for the prevention/treatment of neurological disorders is largely hindered by their complexity and limited knowledge regarding their bioavailability, metabolism and bioactivity in the brain. We recently demonstrated that dietary supplementation with a grape-derived polyphenolic preparation, namely a monomeric-enriched catechin and epicatechin fraction (Mo), significantly improves cognitive function in a mouse model of Alzheimer's disease (AD). We also found that Mo treatment resulted in the accumulation of proanthocyanidin metabolites in the brain at a concentration of ∼400 nM. One of the metabolites identified in the brain following Mo treatment, Metaphenol-A1, was shown to promote basal synaptic transmission and long-term potentiation (LTP) at physiologically relevant concentrations in hippocampal slices through mechanisms associated with cAMP-response-element-binding-protein signaling. C57BL/6 mice were treated with Metaphenol-A1 (7.5 μM) by intranasal route. Brain sections were then harvested at 5, 10, 15, and 60 minutes. Pharmacokinetics and neuronal molecular changes were assessed in the samples collected. The same delivery approach will be applied to the Tg2576 mouse model of AD to assess its effect on cognitive function. We are currently evaluating the pharmacokinetics and brain bioavailability of Metaphenol-A1 delivered via a novel, non-invasive intranasal delivery apparatus. We will also asses the effects of Metaphenol-A1 delivered in this manner on LTP and cognitive function in AD mice. Our study will provide insights into developing a novel, safe approach to directly deliver a bioactive therapeutic agent to the central nervous system for AD prevention/treatment." @default.
- W2083863921 created "2016-06-24" @default.
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- W2083863921 date "2012-07-01" @default.
- W2083863921 modified "2023-09-28" @default.
- W2083863921 title "P3-342: Intranasal delivery of bioactive polyphenol metabolites to prevent and/or treat Alzheimer's disease and other forms of dementia" @default.
- W2083863921 doi "https://doi.org/10.1016/j.jalz.2012.05.1566" @default.
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