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Nasal Spray of Bioactive Polyphenol Metabolites as a Novel Therapy for Alzheimer's Disease and Other Forms of Dementia
Author(s) -
Knable Lindsay Alexis,
Wang Jun,
Ferruzzi Mario G,
Vempati Prashant,
Freire Daniele,
Gong Bing,
Pasinetti Giulio Maria
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.846.3
Subject(s) - long term potentiation , polyphenol , pharmacology , hippocampal formation , cognitive decline , dementia , bioavailability , central nervous system , medicine , neuroscience , nasal administration , chemistry , disease , biochemistry , biology , antioxidant , receptor
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. In this study, we tested whether application of Metaphenol‐A1 via a novel, non‐invasive intranasal delivery apparatus can effectively improve LTP and cognitive function in the 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. Supported by Discretional Funds to GMP.