title: Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25-35 in rats.
abstract: Phosphodiesterase-4 (PDE4) inhibitors prevent the breakdown of the second messenger cAMP and have been demonstrated to improve learning in several animal models of cognition. In this study, we explored the antioxidative effects of rolipram in Alzheimer's disease (AD) by using bilateral Aβ25-35 injection into the hippocampus of rats, which were used as an AD model. Rats received 3 intraperitoneal (i.p.) doses of rolipram (0.1, 0.5 and 1.25 mg/kg) daily after the injection of Aβ25-35 for 25 days. Chronic administration of rolipram prevented the memory impairments induced by Aβ25-35, as assessed using the passive avoidance test and the Morris water maze test. Furthermore, rolipram significantly reduced the oxidative stress induced by Aβ25-35, as evidenced by the decrease in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and restored the reduced GSH levels and superoxide dismutase (SOD) activity. Moreover, western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed that rolipram remarkably upregulated thioredoxin (Trx) and inhibited the inducible nitric oxide synthase/nitric oxide (iNOS/NO) pathway in the hippocampus. These results demonstrated that rolipram improved the learning and memory abilities in an Aβ25-35-induced AD rat model. The mechanism underlying these effects may be due to the noticeable antioxidative effects of rolipram.
authors.affiliation: Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.|The first affiliated hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
authors.forename: Yeye
authors.initials: Y
authors.lastname: Zhuo
authors.affiliation: Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Haibiao
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Ningbo Key Laboratory of Behavioral Neuroscience, 818 Fenghua Road, Ningbo, Zhejiang, 315211, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, 518000, China.
authors.forename: Canmao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Jingang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Pharmacy, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, 518000, China.
authors.forename: Danna
authors.initials: D
authors.lastname: Gan
authors.affiliation: Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China. jpx@smu.edu.cn.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Xu
mesh_terms: D016229:Amyloid beta-Peptides; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001362:Avoidance Learning / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D060825:Cognitive Dysfunction / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments; D058988:Phosphodiesterase 4 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D013879:Thioredoxins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; D058988:Phosphodiesterase 4 Inhibitors; C074636:amyloid beta-protein (25-35); D009569:Nitric Oxide; D013879:Thioredoxins; D052247:Nitric Oxide Synthase Type II; D020889:Rolipram
keywords: Memory; Oxidative stress; Phosphodiesterase-4; Rolipram; β-amyloid