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Inflammatory processes in the central nervous system are thought to contribute to Alzheimer's disease (AD). Chronic administration of nonsteroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of Alzheimer's disease. There are very few studies, however, on the cognitive impact of chronic NSAID administration. The N-methyl-d-aspartate (NMDA) receptor is implicated in learning and memory, and age-related decreases in the NMDA NR2B subunit correlate with memory deficits. Sulindac, an NSAID that is a nonselective cyclooxygenase (COX) inhibitor was chronically administered to aged Fischer 344 rats for 2 months. Sulindac, but not its non-COX active metabolite, attenuated age-related deficits in learning and memory as assessed in the radial arm water maze and contextual fear conditioning tasks. Sulindac treatment also attenuated an age-related decrease in the NR1 and NR2B NMDA receptor subunits and prevented an age-related increase in the pro-inflammatory cytokine, interleukin 1beta (IL-1beta), in the hippocampus. These findings support the inflammation hypothesis of aging and have important implications for potential cognitive enhancing effects of NSAIDs in the elderly.

Original publication

DOI

10.1016/S0197-4580(03)00116-7

Type

Journal article

Journal

Neurobiol Aging

Publication Date

03/2004

Volume

25

Pages

315 - 324

Keywords

Aging, Aldehyde Dehydrogenase, Aldehyde Dehydrogenase, Mitochondrial, Animals, Anti-Inflammatory Agents, Non-Steroidal, Conditioning (Psychology), Disease Models, Animal, Down-Regulation, Encephalitis, Interleukin-1, Male, Maze Learning, Memory Disorders, Neuroprotective Agents, Nootropic Agents, Rats, Rats, Inbred F344, Receptors, N-Methyl-D-Aspartate, Sulindac, Treatment Outcome, Up-Regulation