Abstract

Beta amyloid peptides (Aβ) are known risk factors involved in cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer’s disease (AD). Phosphodiesterase 2 (PDE2) inhibitors increase the intracellular cAMP and/or cGMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE2 mediated neuroapoptotic and neuroinflammatory events, as well as cognitive performance in AD are related to cAMP/cGMP-dependent pathways. The present study investigated how the selective PDE2 inhibitor BAY60-7550 (BAY) affected Aβ-induced learning and memory impairment in two classic rodent models. IL-22 and IL-17, Bax and Bcl-2, PKA/PKG and the brain derived neurotropic factor (BDNF) levels in hippocampus and cortex were detected with immunoblotting assay. The results showed that BAY reversed Aβ-induced cognitive impairment as shown in the water maze test and step-down test. Moreover, BAY treatment reversed the Aβ-induced changes in IL-22 and IL-17 and the ratio of Bax/Bcl-2. Changes in cAMP/cGMP levels, PKA/PKG and BDNF expression were also prevented by BAY. These effects of BAY on memory performance and related neurochemical changes were partially blocked by the PKG inhibitor KT 5823. These findings indicated that the protective effects of BAY against Aβ-induced memory deficits might involve the regulation of neuroinflammation and neuronal apoptotic events.

Details

Title
Inhibition of PDE2 reverses beta amyloid induced memory impairment through regulation of PKA/PKG-dependent neuro-inflammatory and apoptotic pathways
Author
Wang, Li 1 ; Xiaokaiti, Yilixiati 2 ; Wang, Gang 3 ; Xu, Xiaoxiao 4 ; Chen, Ling 3 ; Huang, Xianfeng 5 ; Liu, Li 5 ; Pan, Jianchun 4 ; Hu, Shuqun 6 ; Chen, Zhuoyou 7 ; Xu, Ying 2 

 Clinical Laboratory, Xuzhou No. 1 People’s Hospital, Xuzhou, Jiangsu Province, China 
 Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA 
 Department of Clinical Pharmacy, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China 
 Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China 
 School of Pharmaceutical Engineering & Life Sciences, Changzhou University, Changzhou, Jiangsu Province, China 
 Xuzhou Medical University, Xuzhou, Jiangsu Province, China 
 Changzhou No. 2 People’s Hospital, the Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China 
Pages
1-12
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1955030406
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.