Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation.
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.
Department of Biochemical Science and Biotechnology, National Chia-Yi University, Chia-Yi, Taiwan.
Tai-Chun
TC
Huang
Kwok-Tung
KT
Lu
Yu-Yuan Peter
YY
Wo
Yao-Ju
YJ
Wu
Yi-Ling
YL
Yang
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D000077185:Resveratrol; D045442:Rotarod Performance Test; D013267:Stilbenes / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D020011:Protective Agents; D013267:Stilbenes; D008315:Malondialdehyde; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D000077185:Resveratrol; D019331:NG-Nitroarginine Methyl Ester