Protective Effects of BAY 73-6691, a Selective Inhibitor of Phosphodiesterase 9, on amyloid-β Peptides-Induced Oxidative Stress in In-Vivo and In-Vitro Models of Alzheimer's Disease

Jian Li, Chun-Na Liu, Ning Wei, Xi-Dong Li, Yuan-Yuan Liu, Rui Yang, Yu-Jie Jia

Brain Res. 2016 Jul 1;1642:327-335.

PMID: 27071547

Abstract:

Alzheimer's disease (AD) is accompanied by enhanced oxidative stress and excess free radicals. Phosphodiesterase 9 inhibitors (PDE-9Is) showed memory improving effects in many pharmacological deficit models. However, whether BAY 73-6691 (a selective PDE-9I) may attenuate the oxidative stress during the development of AD is still unclear. For this purpose, primary cultures of SH-SY5Y cells were incubated with 20μM beta-amyloid25-35 (Aβ25-35), followed by exposure to different concentrations (50, 100, 150 and 200μg/ml) of BAY 73-6691. Furthermore, the antioxidant effect of BAY 73-6691 was evaluated in mice subjected to intracerebroventricular injection of Aβ25-35 (day 0) and treatment with BAY 73-6691 by intraperitoneal injection once daily (days 1-10). Our results elucidated that treatment with BAY 73-6691 attenuated the Aβ25-35-induced cytotoxicity and oxidative stress in SH-SY5Y cells. In vivo, BAY 73-6691 protected Aβ25-35-induced oxidative damage in hippocampus, associated with the attenuation of impairments in hippocampal neurons. Administration of BAY 73-6691 improved learning and memory in the Morris water maze test, and restored several hippocampal memory-associated proteins. Our study identified a neuroprotective role for BAY 73-6691 against Aβ25-35-induced oxidative stress in vivo and in vitro, harboring therapeutic potential for the treatment of AD by alleviating the impairments in spatial memory and hippocampal neurons.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP794568926	BAY 73-6691		794568-92-6	Price