Journal
NEUROBIOLOGY OF AGING
Volume 25, Issue 3, Pages 315-324Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0197-4580(03)00116-7
Keywords
aging; memory; nonsteroidal anti-inflammatory drug; NSAID; N-methyl-D-aspartate receptor; NMDA-R; cytokine; neurodegeneration; water maze; fear conditioning; hippocampus; interleukin 1 beta
Categories
Funding
- NIA NIH HHS [AG04418, AG00961] Funding Source: Medline
Ask authors/readers for more resources
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. (C) 2003 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available