NDLI: Phosphodiesterase-5 inhibitor sildenafil prevents neuroinflammation, lowers beta-amyloid levels and improves cognitive performance in APP/PS1 transgenic mice

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Phosphodiesterase-5 inhibitor sildenafil prevents neuroinflammation, lowers beta-amyloid levels and improves cognitive performance in APP/PS1 transgenic mice

Content Provider	Semantic Scholar
Author	Zhang, Junfang Guo, Jiejie Zhao, Xin Chen, Zhuoyou Wang, Chuang
Copyright Year	2013
Abstract	Memory deficit is a marker of Alzheimer's disease (AD) that has been highly associated with the dysfunction of cyclic GMP (cGMP) signaling and an ongoing inflammatory process. Phosphodiesterase-5 (PDE5) inhibitors prevent the breakdown of cGMP and are currently studied as a possible target for cognitive enhancement. However, it is still unknown whether inhibition of PDE5 reversed β-amyloid peptide (Aβ)-induced neuroinflammation in APP/PS1 transgenic (Tg APP/PS1) mice. The present study evaluated the cognitive behaviors, inflammatory mediators, and cGMP/PKG/pCREB signaling in 15-month-old Tg APP/PS1 mice and age-matched wild-type (WT) mice that were treated with PDE5 inhibitor sildenafil and the inhibitor of cGMP-dependent protein kinase Rp-8-Br-PET-cGMPS. In comparison with WT mice, Tg APP/PS1 mice were characterized by impaired cognitive ability, neuroinflammatory response, and down-regulated cGMP signaling. Sildenafil reversed these memory deficits and cGMP/PKG/pCREB signaling dysfunction; it also reduced both the soluble Aβ1-40 and Aβ1-42 levels in the hippocampus. These effects of sildenafil were prevented by intra-hippocampal infusion of the Rp-8-Br-PET-cGMPS. These results suggest that sildenafil could restore cognitive deficits in Tg APP/PS1 mice by the regulation of PKG/pCREB signaling, anti-inflammatory response and reduction of Aβ levels.
Starting Page	230
Ending Page	237
Page Count	8
File Format	PDF HTM / HTML
DOI	10.1016/j.bbr.2013.05.017
PubMed reference number	23685322
Journal	Medline
Volume Number	250
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S016643281300288X
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S016643281300288X?dgcid=api_sd_search-api-endpoint
Alternate Webpage(s)	https://doi.org/10.1016/j.bbr.2013.05.017
Journal	Behavioural Brain Research
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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