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Icariin, a phoshphodiesterase-5 inhibitor, improves learning and memory in APP/PS1 transgenic mice by stimulation of NO/cGMP signalling
| Content Provider | Scilit |
|---|---|
| Author | Jin, Feng Gong, Qi-Hai Xu, Ya-Sha Wang, Li-Na Jin, Hai Li, Fei Li, Li-Sheng Ma, Yue-Ming Shi, Jing-Shan |
| Copyright Year | 2014 |
| Description | Phosphodiesterase-5 (PDE5) inhibitors are predominantly used in the treatment of erectile dysfunction, and have been recently shown to have a potential therapeutic effect for the treatment of Alzheimer's disease (AD) through stimulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling by elevating cGMP, which is a secondary messenger involved in processes of neuroplasticity. In the present study, the effects of a PDE5 inhibitor, icarrin (ICA), on learning and memory as well as the pathological features in APP/PS1 transgenic AD mice were investigated. Ten-month-old APP/PS1 transgenic mice overexpressing human amyloid precursor protein (APP695swe) and presenilin 1 (PS1-dE9) were given ICA (30 and 60 mg/kg) or sildenafil (SIL) (2 mg/kg), age-matched wild-type (WT) mice were given ICA (60 mg/kg), and APP/PS1 and WT control groups were given an isovolumic vehicle orally twice a day for four months. Results demonstrated that ICA treatments significantly improved learning and memory of APP/PS1 transgenic mice in Y-maze tasks. The amyloid precursor protein (APP), amyloid-beta (Aβ1-40/42) and PDE5 mRNA and/or protein levels were increased in the hippocampus and cortex of APP/PS1 mice, and ICA treatments decreased these physiopathological changes. Furthermore, ICA-treated mice showed an increased expression of three nitric oxide synthase (NOS) isoforms at both mRNA and protein levels, together with increased NO and cGMP levels in the hippocampus and cortex of mice. These findings demonstrate that ICA improves learning and memory functions in APP/PS1 transgenic mice possibly through the stimulation of NO/cGMP signalling and co-ordinated induction of NOS isoforms. |
| Related Links | https://academic.oup.com/ijnp/article-pdf/17/6/871/2033564/17-6-871.pdf |
| Ending Page | 881 |
| Page Count | 11 |
| Starting Page | 871 |
| DOI | 10.1017/s1461145713001533 |
| Journal | International Journal of Neuropsychopharmacology |
| Issue Number | 06 |
| Volume Number | 17 |
| Language | English |
| Publisher | Cambridge University Press (CUP) |
| Publisher Date | 2014-06-01 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Neuropsychopharmacology ps1 Transgenic cgmp cgmp Signalling ps1 |
| Content Type | Text |
| Resource Type | Article |
