摘要: In Alzheimer's disease (AD), activated microglia invade and surround beta-amyloid plaques, possibly contributing to the aggregation of amyloid beta (A beta), which affect the survival of neurons and lead to memory loss. Phosphodiesterase-5 (PDE-5) inhibitors have recently been shown a potential therapeutic effect on AD. In this study, the effects of yonkenafil (yonk), a novel PDE-5 inhibitor, on cognitive behaviors as well as the pathological features in transgenic AD mice were investigated. Seven-month-old APP/PSI transgenic mice were treated with yonk (2, 6, or 18 mg/kg, intraperitoneal injection (i.p.)) or sildenafil (slid) (6 mg/kg, i.p.) daily for 3 months and then behavioral tests were performed. The results demonstrated that yonk improved nesting-building ability, ameliorated working memory deficits in the Y-maze tasks, and significantly improved learning and memory function in the Morris water maze (MWM) tasks. In addition, yonk reduced the area of A beta plaques, and inhibited over-activation of microglia and astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain region of APP/PSI mice, indicated by increased BrdU(+)/NeuN(+) and BrdU(+)/DCX+ cells compared to vehicle-treated transgenic mice. These results suggest that yonk could rescue cognitive deficits by ameliorated amyloid burden through regulating APP processing, inhibited the over-activation of microglia and astrocytes as well as restored neurogenesis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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期刊:
MECHANISMS OF AGEING AND DEVELOPMENT
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分类:
生物学
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生物物理学
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细胞生物学
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引用:
ChinaXiv:201605.01318
(或此版本
ChinaXiv:201605.01318V1)
doi:10.12074/201605.01318
CSTR:32003.36.ChinaXiv.201605.01318.V1
- 推荐引用方式:
Zhu, Lei,Yang, Jing-Yu,Dong, Ying-Xu,Liu, Yang,Miao, Feng-Rong,Xue, Hong,Wu, Chun-Fu,Xue, Hong,Xue, Xue,Wang, Yong-Feng.(2016).A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model.MECHANISMS OF AGEING AND DEVELOPMENT.[ChinaXiv:201605.01318]
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