Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology.
Both oxidative damage and inflammation have been implicated in age-related neurodegenerative diseases including Alzheimer's Disease (AD). The yellow curry spice, curcumin, has both antioxidant and anti-inflammatory activities which confer significant protection against neurotoxic and genotoxic agents. We used 22 month Sprague-Dawley (SD) rats to compare the effects of the conventional NSAID, ibuprofen, and curcumin for their ability to protect against amyloid beta-protein (Abeta)-induced damage. Lipoprotein carrier-mediated, intracerebroventricular infusion of Abeta peptides induced oxidative damage, synaptophysin loss, a microglial response and widespread Abeta deposits. Dietary curcumin (2000 ppm), but not ibuprofen, suppressed oxidative damage (isoprostane levels) and synaptophysin loss. Both ibuprofen and curcumin reduced microgliosis in cortical layers, but curcumin increased microglial labeling within and adjacent to Abeta-ir deposits. In a second group of middle-aged female SD rats, 500 ppm dietary curcumin prevented Abeta-infusion induced spatial memory deficits in the Morris Water Maze and post-synaptic density (PSD)-95 loss and reduced Abeta deposits. Because of its low side-effect profile and long history of safe use, curcumin may find clinical application for AD prevention.
Frautschy
S A
SA
VAGLAHS-Sepulveda GRECC, Departments of Medicine and Neurology, UCLA, 16111 Plummer Street, North Hills, CA, USA. frautsch@ucla.edu
Hu
W
W
Kim
P
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Miller
S A
SA
Chu
T
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Harris-White
M E
ME
Cole
G M
GM
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain; D001923:Brain Chemistry; D003072:Cognition Disorders / Q000139:chemically induced* / Q000473:pathology / Q000523:psychology; D003474:Curcumin / Q000494:pharmacology; D004032:Diet; D004797:Enzyme-Linked Immunosorbent Assay; D007052:Ibuprofen / Q000494:pharmacology; D007090:Image Interpretation, Computer-Assisted; D007150:Immunohistochemistry; D007267:Injections; D018782:Maze Learning / Q000187:drug effects; D018832:Molecular Chaperones / Q000737:chemistry; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D010636:Phenols / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000473:pathology; D016708:Synaptophysin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018832:Molecular Chaperones; D009498:Neurotoxins; D010446:Peptide Fragments; D010636:Phenols; D016708:Synaptophysin; C075222:amyloid beta-protein (1-42); D003474:Curcumin; D007052:Ibuprofen