Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging. (6th March 2017)

• Record Type: Journal Article
• Authors: Márquez Loza, Alejandra; Elias, Valerie; Wong, Carmen P.; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R.
• Is Part Of: Neuroscience. Volume 344(2017)
• Page Start: 276
• Page End: 292
• Publication Date: 2017-03-06
• Subjects: N-methyl-d-aspartate receptor -- executive function -- anti-inflammatory -- aging; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.12.041
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Ibuprofen enhanced executive function more than memory in a short-term memory task. Ibuprofen decreased expression of several NMDA receptor subunits across adult aging. Ibuprofen increased expression of GluN1-3 splice form mRNA and C2′ cassette protein in frontal lobes regardless of age. Ibuprofen did not alter expression of pro-inflammatory cytokines, but reduced gliosis in frontal cortex of aged mice. Enhancement in executive function was related to increased GluN1-3 mRNA and decreased gliosis. 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 26 months) were fed ibuprofen (375 ppm) in NIH31 diet or diet alone for 6 weeks 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.