A Pro-Inflammatory Agent, Lipopolysaccharide, Can Mimic the Effects of Aging on Spatial Reference Memory Public Deposited

http://ir.library.oregonstate.edu/concern/undergraduate_thesis_or_projects/fb494b180

Presentation entitled : A Pro-Inflammatory Agent, Lipopolysaccharide, Can Mimic the Effects of Aging on Spatial Reference Memory / by Emily R. Escobedo and Kathy R. Magnusson

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  • Humans and rodents experience declines in reference (long-term) and working (short-term) memory and cognitive flexibility during the aging process. Aging changes in GluN1 and GluN2B subunits of N-methyl-D-aspartate (NMDA) receptors show a relationship to both reference and working memory deficits. Sulindac, an anti-inflammatory drug, enhances working memory and NMDA receptor subunit expression in rats. The hypothesis addressed in the present study was that inflammation plays a role in NMDA receptor aging and memory declines. The question addressed was whether a pro-inflammatory treatment in young mice would produce the same changes in memory and NMDA receptor expression as aging. Lipopolysaccharide (LPS) was the pro-inflammatory treatment that was used to induce inflammation in 3 month old mice by surgical procedure. Male C57BL/6 mice (3 month old) were randomly assigned to 3 treatment groups, lipopolysaccharide (LPS), saline, or non-surgical. Non-surgical (24 month old) mice were also included. These different types of treatment were then randomly assigned to behaviorally characterized or naïve. The behaviorally characterized animals were behaviorally tested with the Morris water maze. The naïve animals were housed for the same amount of time being. The surgical procedure consisted of cannulas that were attached to osmotic pumps, then implanted into the lateral ventricles of the brain for 3 weeks in order to inject all of the LPS or saline solution. One week after pumps were removed, behavioral testing was performed with the Morris water maze. LPS-treated young (cumulative proximity (cm): 6287 ± 625; RANOVA & Fisher’s LSD) performed significantly worse than saline young (Mean: 4565 ± 352) and similarly to old mice (Mean: 7519 ± 389) in reference memory place trials. LPS treated young (average proximity (cm): 40 ± 1.4) performed similarly to saline young (35 ± 1.3) and old (45± 1.5) performed the poorest in probe trials for reference memory. LPS didn’t appear to have any effect on reversal, working memory, or cued trials. The average swim speed for reference memory and cued trials showed that the LPS treated mice were the fastest swimmers, suggesting that any deficits were not due to poor motor ability. In situ hybridization for the NMDA subunits GluN2B, GluN2A, GluN1 and receptor autoradiography, using the agonist glutamate and the competitive antagonist [(±)-2-carboxypiperazin-4-yl] propyl-1-phosphonic acid (CPP), were performed on sections from C57Bl/6 mice There were no significant effects of LPS on mRNA densities for the GluN2B, GluN2A, or GluN1 subunits. In conclusion, stimulating inflammation in a young brain produced only some of the memory deficits seen in aging.
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  • description.provenance : Made available in DSpace on 2014-07-22T22:08:40Z (GMT). No. of bitstreams: 2 Escobedo thesis.signed.pdf: 714746 bytes, checksum: 4dd066928d1004438d573ca86c280f27 (MD5) Escobedo seminar presentation.pdf: 1377499 bytes, checksum: e6f85532f0ccba6440505294c24185ae (MD5)
  • description.provenance : Submitted by Wanda Crannell (brr@oregonstate.edu) on 2014-07-22T21:37:09Z No. of bitstreams: 2 Escobedo thesis.signed.pdf: 714746 bytes, checksum: 4dd066928d1004438d573ca86c280f27 (MD5) Escobedo seminar presentation.pdf: 1377499 bytes, checksum: e6f85532f0ccba6440505294c24185ae (MD5)
  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2014-07-22T22:08:40Z (GMT) No. of bitstreams: 2 Escobedo thesis.signed.pdf: 714746 bytes, checksum: 4dd066928d1004438d573ca86c280f27 (MD5) Escobedo seminar presentation.pdf: 1377499 bytes, checksum: e6f85532f0ccba6440505294c24185ae (MD5)

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