PT  - JOURNAL ARTICLE
AU  - Wang, Jun
AU  - Ferruzzi, Mario G.
AU  - Ho, Lap
AU  - Blount, Jack
AU  - Janle, Elsa M.
AU  - Gong, Bing
AU  - Pan, Yong
AU  - Gowda, G. A. Nagana
AU  - Raftery, Daniel
AU  - Arrieta-Cruz, Isabel
AU  - Sharma, Vaishali
AU  - Cooper, Bruce
AU  - Lobo, Jessica
AU  - Simon, James E.
AU  - Zhang, Chungfen
AU  - Cheng, Alice
AU  - Qian, Xianjuan
AU  - Ono, Kenjiro
AU  - Teplow, David B.
AU  - Pavlides, Constantine
AU  - Dixon, Richard A.
AU  - Pasinetti, Giulio M.
TI  - Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment
AID  - 10.1523/JNEUROSCI.6437-11.2012
DP  - 2012 Apr 11
TA  - The Journal of Neuroscience
PG  - 5144--5150
VI  - 32
IP  - 15
4099  - http://www.jneurosci.org/content/32/15/5144.short
4100  - http://www.jneurosci.org/content/32/15/5144.full
SO  - J. Neurosci.2012 Apr 11; 32
AB  - 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 as well as by limited knowledge regarding their bioavailability, metabolism, and bioactivity, especially in the brain. We recently demonstrated that dietary supplementation with a specific grape-derived polyphenolic preparation (GP) significantly improves cognitive function in a mouse model of Alzheimer's disease (AD). GP is comprised of the proanthocyanidin (PAC) catechin and epicatechin in monomeric (Mo), oligomeric, and polymeric forms. In this study, we report that following oral administration of the independent GP forms, only Mo is able to improve cognitive function and only Mo metabolites can selectively reach and accumulate in the brain at a concentration of ∼400 nm. Most importantly, we report for the first time that a biosynthetic epicatechin metabolite, 3′-O-methyl-epicatechin-5-O-β-glucuronide (3′-O-Me-EC-Gluc), one of the PAC metabolites identified in the brain following Mo treatment, promotes basal synaptic transmission and long-term potentiation at physiologically relevant concentrations in hippocampus slices through mechanisms associated with cAMP response element binding protein (CREB) signaling. Our studies suggest that select brain-targeted PAC metabolites benefit cognition by improving synaptic plasticity in the brain, and provide impetus to develop 3′-O-Me-EC-Gluc and other brain-targeted PAC metabolites to promote learning and memory in AD and other forms of dementia.