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Inhibition of PDE2 reverses beta amyloid induced memory impairment through regulation of PKA/PKG-dependent neuro-inflammatory and apoptotic pathways.

Inhibition of PDE2 reverses beta amyloid induced memory impairment through regulation of PKA/PKG-dependent neuro-inflammatory and apoptotic pathways.
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Wang L, Xiaokaiti Y, Wang G, Xu X, Chen L, Huang X, Liu L, Pan J, Hu S, Chen Z, Xu Y,


Wang L, Xiaokaiti Y, Wang G, Xu X, Chen L, Huang X, Liu L, Pan J, Hu S, Chen Z, Xu Y, (click to view)

Wang L, Xiaokaiti Y, Wang G, Xu X, Chen L, Huang X, Liu L, Pan J, Hu S, Chen Z, Xu Y,

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Scientific reports 2017 09 217(1) 12044 doi 10.1038/s41598-017-08070-2
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.

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