Inhibition of Phosphodiesterase-4 Reverses the Cognitive Dysfunction and Oxidative Stress Induced by Aβ25-35 in Rats

Overview

Journal Metab Brain Dis

Publisher Springer

Specialties Endocrinology
Neurology

Date 2016 Feb 28

PMID 26920899

Citations 10

Authors

Yeye Zhuo

Haibiao Guo

Yufang Cheng

Chuang Wang

Canmao Wang

Jingang Wu

Zhengqiang Zou

Danna Gan

Yiwen Li

Jiangping Xu

Affiliations

Soon will be listed here.

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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