Dexibuprofen (S(+)-isomer ibuprofen) reduces microglial activation and impairments of spatial working memory induced by chronic lipopolysaccharide infusion.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been proposed as a therapeutics to reduce the risk of Alzheimer's disease (AD). The present study shows that the peripheral administration of dexibuprofen (S(+)-isomer ibuprofen), which causes less gastric damage and has better anti-inflammatory effects than ibuprofen, reduces the microglial activation in the cortex and hippocampus, and reduces the phosphorylation of extracellular signal-regulated kinases in the hippocampus, which has been induced by chronic infusion of lipopolysaccharide (LPS) into the fourth ventricle of Wistar rats. The effects of dexibuprofen on impairments of spatial working memory induced by LPS infusions were measured with a trial-unique matching-to-place task in a water maze which assessed memory for place information over varying delays. When performing the water maze task, the rats with the LPS infusions showed spatial working memory impairments relative to the rats with the artificial cerebrospinal fluid. Daily administrations of dexibuprofen reduced the spatial working memory impairment induced by the chronic LPS infusion. The results indicate that NSAID treatments using dexibuprofen significantly attenuate the processes that drive the pathology associated with AD and that this process may involve the suppression of microglial activation.
Jin
Da-Qing
DQ
Graduate Program in Neuroscience, Institute for Brain Science and Technology (IBST), Inje University, Daejeon, South Korea.
Sung
Jin-Young
JY
Hwang
Yoo Kyeong
YK
Kwon
Kyoung Ja
KJ
Han
Seol-Heui
SH
Min
Sun Seek
SS
Han
Jung-Soo
JS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology; D007216:Indoprofen / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D017628:Microglia / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D007216:Indoprofen; D048049:Extracellular Signal-Regulated MAP Kinases