title: The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling.
abstract: Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Aβ) are known to involve cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Activation of cAMP and/or cGMP activities can improve memory performance and decrease the neuroinflammation and apoptosis. However, it remains unknown whether the memory enhancing effect of resveratrol on AD associated cognitive disorders is related to the inhibition of phosphodiesterase 4 (PDE4) subtypes and subsequent increases in intracellular cAMP and/or cGMP activities. This study investigated the effect of resveratrol on Aβ1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Aβ1-42 into bilateral CA1 subregions displayed learning and memory impairment, as evidenced by reduced memory acquisition and retrieval in the water maze and retention in the passive avoidance tasks; it was also significant that neuroinflammatory and pro-apoptotic factors were increased in Aβ1-42-treated mice. Aβ1-42-treated mice also increased in PDE4A, 4B and 4D expression, and decreased in PKA level. However, PKA inhibitor H89, but not PKG inhibitor KT5823, prevented resveratrol's effects on these parameters. Resveratrol also reversed Aβ1-42-induced decreases in phosphorylated cAMP response-element binding protein (pCREB), brain derived neurotrophic factor (BDNF) and anti-apoptotic factor BCl-2 expression, which were reversed by H89. These findings suggest that resveratrol reversing Aβ-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling.
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Thyroid Surgery, Kunming Medical University Affiliated First People's Hospital, Kunming, Yunnan Province, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Neurology, Lianyungang Second People's Hospital, Lianyungang, Jiangsu Province, China.
authors.forename: Jiechun
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, Jiangsu Province, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Weijie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Thyroid Surgery, Kunming Medical University Affiliated First People's Hospital, Kunming, Yunnan Province, China.
authors.forename: Ruochuan
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, Jiangsu Province, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Yingcong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Behavioral Medicine and Psychiatry, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Han-Ting
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: O'Donnell
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000008:administration & dosage; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004195:Disease Models, Animal; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000008:administration & dosage; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D058988:Phosphodiesterase 4 Inhibitors; D013267:Stilbenes; C075222:amyloid beta-protein (1-42); D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D000077185:Resveratrol
keywords: Gerotarget; PDE4; apoptosis; beta amyloid peptide; learning and memory; resveratrol