The effects of a novel NSAID on chronic neuroinflammation are age dependent.
Chronic inflammation may play an important role in the pathogenesis of Alzheimer's disease (AD). The present study compared the effects of chronic neuroinflammation, produced by infusion of lipopolysaccharide (LPS) into the fourth ventricle, upon memory in young, adult, and old rats. Nonsteroidal anti-inflammatory drug (NSAID) therapy may delay the onset of AD. We show that NO-Flurbiprofen (NFP), a novel NSAID that lacks gastrointestinal side effects, attenuated the neuroinflammatory reaction and reduced the inflammation-induced memory deficit. Chronic LPS infusions impaired performance of young rats but not adult or old rats. Treatment with NFP improved the performance of LPS-infused young rats, but not LPS-infused adult or old rats. LPS infusions increased the number of activated microglia in young and adult rats but not old rats. NFP treatment attenuated the effects of LPS upon microglia activation in young and adult rats, but not old rats. The results suggest that NSAID therapies designed to influence the onset of AD should be initiated in adults before age-associated inflammatory processes within the brain have a chance to develop.
Hauss-Wegrzyniak
B
B
Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, 85724, USA.
Vraniak
P
P
Wenk
G L
GL
D000367:Age Factors; D000375:Aging / Q000187:drug effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D018891:Dentate Gyrus / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy*; D005480:Flurbiprofen / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008070:Lipopolysaccharides; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D017628:Microglia / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D013028:Space Perception / Q000187:drug effects; D013702:Temporal Lobe / Q000187:drug effects / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D005480:Flurbiprofen