Format

Send to

Choose Destination
Mech Ageing Dev. 2015 Sep;150:34-45. doi: 10.1016/j.mad.2015.07.002. Epub 2015 Jul 19.

A novel phosphodiesterase-5 Inhibitor: Yonkenafil modulates neurogenesis, gliosis to improve cognitive function and ameliorates amyloid burden in an APP/PS1 transgenic mice model.

Author information

1
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, China.
2
Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, PR China.
3
Zhuhai Oxforston PharmTech Co. Ltd, Tangjiawan, 519085 Zhuhai, China.
4
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, China; Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Electronic address: hxue@ust.hk.
5
Department of Pharmacology, Shenyang Pharmaceutical University, Box 31, 103 Wenhua Road, 110016 Shenyang, China. Electronic address: wucf@syphu.edu.cn.

Abstract

In Alzheimer's disease (AD), activated microglia invade and surround β-amyloid plaques, possibly contributing to the aggregation of amyloid β (Aβ), 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/PS1 transgenic mice were treated with yonk (2, 6, or 18 mg/kg, intraperitoneal injection (i.p.)) or sildenafil (sild) (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 Aβ plaques, and inhibited over-activation of microglia and astrocytes. Furthermore, yonk increased neurogenesis in the dentate granule brain region of APP/PS1 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.

KEYWORDS:

Cognitive; Microglia; Neurogenesis; Yonkenafil; β-amyloid

PMID:
26200391
DOI:
10.1016/j.mad.2015.07.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center