RT Journal Article
SR Electronic
T1 Brain-Targeted Proanthocyanidin Metabolites for Alzheimer's Disease Treatment
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5144
OP 5150
DO 10.1523/JNEUROSCI.6437-11.2012
VO 32
IS 15
A1 Wang, Jun
A1 Ferruzzi, Mario G.
A1 Ho, Lap
A1 Blount, Jack
A1 Janle, Elsa M.
A1 Gong, Bing
A1 Pan, Yong
A1 Gowda, G. A. Nagana
A1 Raftery, Daniel
A1 Arrieta-Cruz, Isabel
A1 Sharma, Vaishali
A1 Cooper, Bruce
A1 Lobo, Jessica
A1 Simon, James E.
A1 Zhang, Chungfen
A1 Cheng, Alice
A1 Qian, Xianjuan
A1 Ono, Kenjiro
A1 Teplow, David B.
A1 Pavlides, Constantine
A1 Dixon, Richard A.
A1 Pasinetti, Giulio M.
YR 2012
UL http://www.jneurosci.org/content/32/15/5144.abstract
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.