Abstract
Alzheimer disease (AD) is an age-dependent neurodegenerative disease characterized by the formation of β–amyloid (Aβ)-containing senile plaque. The disease could be induced by the administration of Aβ peptide, which was also known to upregulate inducible nitric oxide synthase (iNOS) and stimulate neuronal apoptosis. The present study is aimed to elucidate the cellular effect of resveratrol, a natural phytoestrogen with neuroprotective activities, on Aβ-induced hippocampal neuron loss and memory impairment. On adult Sprague-Dawley rats, we found the injection of Aβ could result in a significant impairment in spatial memory, a marked increase in the cellular level of iNOS and lipid peroxidation, and an apparent decrease in the expression of heme oxygenase-1 (HO-1). By combining the treatment with Aβ, resveratrol was able to confer a significant improvement in spatial memory, and protect animals from Aβ-induced neurotoxicity. These neurological protection effects of resveratrol were associated with a reduction in the cellular levels of iNOS and lipid peroxidation and an increase in the production of HO-1. Moreover, the similar neurological and cellular response were also observed when Aβ treatment was combined with the administration of a NOS inhibitor, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME). These findings strongly implicate that iNOS is involved in the Aβ-induced lipid peroxidation and HO-1 downregulation, and resveratrol protects animals from Aβ-induced neurotoxicity by suppressing iNOS production.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disorder, which could lead to a severe dementia and affect multiple cognitive and behavioral functions
Such over-aggregation of hippocampal Amyloid b protein (Ab) did not occur if the rats were injected with resveratrol alone
Resveratrol treatment reversed the Ab-induced inducible nitric oxide synthase (iNOS) overexpression, and L-NAME conferred a similar but more profound effect, as that of resveratrol, on iNOS production suppression. These results clearly demonstrated that resveratrol could effectively suppress iNOS expression that was stimulated by Ab
Summary
Alzheimer’s disease (AD) is a neurodegenerative disorder, which could lead to a severe dementia and affect multiple cognitive and behavioral functions. Due to the worldwide aging problem, AD has accounted for about 60% of all dementia [1] and has obviously become a serious health problem to be coped with. The precise mechanism of Ab-induced neuronal death and AD is not well understood, Ab neurotoxicity has been connected with various cellular impacts, including Ca2+ influx, glutamate accumulation, and oxidative stress [4]. Since the aging process is typically associated with an augment in the reactive oxygen species (ROS) production together with a parallel decline in the ability to defend ROS attack, oxidative stress is speculated to be the primary causative event that contributes to the progress of AD [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
