TY - JOUR T1 - Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment JF - The Journal of Neuroscience JO - J. Neurosci. SP - 5144 LP - 5150 DO - 10.1523/JNEUROSCI.6437-11.2012 VL - 32 IS - 15 AU - Jun Wang AU - Mario G. Ferruzzi AU - Lap Ho AU - Jack Blount AU - Elsa M. Janle AU - Bing Gong AU - Yong Pan AU - G. A. Nagana Gowda AU - Daniel Raftery AU - Isabel Arrieta-Cruz AU - Vaishali Sharma AU - Bruce Cooper AU - Jessica Lobo AU - James E. Simon AU - Chungfen Zhang AU - Alice Cheng AU - Xianjuan Qian AU - Kenjiro Ono AU - David B. Teplow AU - Constantine Pavlides AU - Richard A. Dixon AU - Giulio M. Pasinetti Y1 - 2012/04/11 UR - http://www.jneurosci.org/content/32/15/5144.abstract N2 - 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. ER -