PMID- 26980711 OWN - NLM STAT- MEDLINE DCOM- 20170209 LR - 20181202 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 7 IP - 14 DP - 2016 Apr 5 TI - The effect of resveratrol on beta amyloid-induced memory impairment involves inhibition of phosphodiesterase-4 related signaling. PG - 17380-92 LID - 10.18632/oncotarget.8041 [doi] AB - Resveratrol, a natural polyphenol found in red wine, has wide spectrum of pharmacological properties including antioxidative and antiaging activities. Beta amyloid peptides (Abeta) 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 Abeta1-42-induced cognitive impairment and the participation of PDE4 subtypes related cAMP or cGMP signaling. Mice microinfused with Abeta1-42 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 Abeta1-42-treated mice. Abeta1-42-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 Abeta1-42-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 Abeta-induced learning and memory disorder may involve the regulation of neuronal inflammation and apoptosis via PDE4 subtypes related cAMP-CREB-BDNF signaling. FAU - Wang, Gang AU - Wang G AD - Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China. FAU - Chen, Ling AU - Chen L AD - Department of Clinical Pharmacy, Hangzhou First People's Hospital, Hangzhou, Zhejiang Province, China. FAU - Pan, Xiaoyu AU - Pan X AD - Department of Thyroid Surgery, Kunming Medical University Affiliated First People's Hospital, Kunming, Yunnan Province, China. FAU - Chen, Jiechun AU - Chen J AD - Department of Neurology, Lianyungang Second People's Hospital, Lianyungang, Jiangsu Province, China. FAU - Wang, Liqun AU - Wang L AD - School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, Jiangsu Province, China. FAU - Wang, Weijie AU - Wang W AD - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America. FAU - Cheng, Ruochuan AU - Cheng R AD - Department of Thyroid Surgery, Kunming Medical University Affiliated First People's Hospital, Kunming, Yunnan Province, China. FAU - Wu, Fan AU - Wu F AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Feng, Xiaoqing AU - Feng X AD - School of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, Jiangsu Province, China. FAU - Yu, Yingcong AU - Yu Y AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China. FAU - Zhang, Han-Ting AU - Zhang HT AD - Department of Behavioral Medicine and Psychiatry, West Virginia University, Morgantown, West Virginia, United States of America. FAU - O'Donnell, James M AU - O'Donnell JM AD - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America. FAU - Xu, Ying AU - Xu Y AD - Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, United States of America. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 RN - 0 (Amyloid beta-Peptides) RN - 0 (Peptide Fragments) RN - 0 (Phosphodiesterase 4 Inhibitors) RN - 0 (Stilbenes) RN - 0 (amyloid beta-protein (1-42)) RN - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4) RN - Q369O8926L (Resveratrol) SB - IM MH - Alzheimer Disease/drug therapy/physiopathology/psychology MH - Amyloid beta-Peptides/administration & dosage MH - Animals MH - Apoptosis/drug effects MH - Cyclic Nucleotide Phosphodiesterases, Type 4/*metabolism MH - Disease Models, Animal MH - Male MH - Memory Disorders/*drug therapy/etiology MH - Mice MH - Mice, Inbred ICR MH - Peptide Fragments/administration & dosage MH - Phosphodiesterase 4 Inhibitors/*pharmacology MH - Resveratrol MH - Signal Transduction/drug effects MH - Stilbenes/*pharmacology PMC - PMC4951219 OTO - NOTNLM OT - Gerotarget OT - PDE4 OT - apoptosis OT - beta amyloid peptide OT - learning and memory OT - resveratrol COIS- CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest. EDAT- 2016/03/17 06:00 MHDA- 2017/02/10 06:00 PMCR- 2016/04/05 CRDT- 2016/03/17 06:00 PHST- 2015/11/18 00:00 [received] PHST- 2016/02/21 00:00 [accepted] PHST- 2016/03/17 06:00 [entrez] PHST- 2016/03/17 06:00 [pubmed] PHST- 2017/02/10 06:00 [medline] PHST- 2016/04/05 00:00 [pmc-release] AID - 8041 [pii] AID - 10.18632/oncotarget.8041 [doi] PST - ppublish SO - Oncotarget. 2016 Apr 5;7(14):17380-92. doi: 10.18632/oncotarget.8041.