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01-08-2016 | Original Article

Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25–35 in rats

Authors: Yeye Zhuo, Haibiao Guo, Yufang Cheng, Chuang Wang, Canmao Wang, Jingang Wu, Zhengqiang Zou, Danna Gan, Yiwen Li, Jiangping Xu

Published in: Metabolic Brain Disease | Issue 4/2016

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.

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Title: Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25–35 in rats
Authors: Yeye Zhuo
Haibiao Guo
Yufang Cheng
Chuang Wang
Canmao Wang
Jingang Wu
Zhengqiang Zou
Danna Gan
Yiwen Li
Jiangping Xu
Publication date: 01-08-2016
Publisher: Springer US
Published in: Metabolic Brain Disease / Issue 4/2016
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-016-9814-1

At a glance: The STEP trials

Springer Medicine

Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25–35 in rats

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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