title: Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.
abstract: Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2' cassettes in the hippocampus. GluN1-3 splice form mRNA and C2' cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation.
authors.affiliation: Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. Electronic address: Alejandra_MarquezLoza@hms.harvard.edu.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Márquez Loza
authors.affiliation: Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. Electronic address: Valerie.Elias@oregonstate.edu.
authors.forename: Valerie
authors.initials: V
authors.lastname: Elias
authors.affiliation: School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. Electronic address: Carmen.Wong@oregonstate.edu.
authors.forename: Carmen P
authors.initials: CP
authors.lastname: Wong
authors.affiliation: Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; School of Biological and Population Health Sciences, Oregon State University, Corvallis, OR 97331, USA. Electronic address: Emily.Ho@oregonstate.edu.
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
authors.affiliation: Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. Electronic address: michelle.bermudez@emory.edu.
authors.forename: Michelle
authors.initials: M
authors.lastname: Bermudez
authors.affiliation: Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA. Electronic address: Kathy.Magnusson@oregonstate.edu.
authors.forename: Kathy R
authors.initials: KR
authors.lastname: Magnusson
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D017398:Alternative Splicing; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D056344:Executive Function / Q000187:drug effects / Q000502:physiology; D005911:Gliosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007052:Ibuprofen / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology; D008810:Mice, Inbred C57BL; D018697:Nootropic Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018697:Nootropic Agents; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D007052:Ibuprofen
keywords: N-methyl-d-aspartate receptor; aging; anti-inflammatory; executive function