A pro-inflammatory agent, lipopolysaccharide, can mimic the effects of aging on spatial reference memory
E. R. ESCOBEDO and K. R. Magnusson, Dept. of Biomedical Sciences, Coll. of Vet. Med., Linus Pauling Institute, Oregon State University, Corvallis, OR 97331
Humans and rodents experience declines in reference (long-term), 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.
Male C57BL/6 mice (3 month old) were randomly assigned to 2 treatment groups, lipopolysaccharide (LPS) or saline. Non-surgical (24 month old) mice were also included. Cannulas attached to osmotic pumps were implanted into the lateral ventricles of the brain for 3 weeks. 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 similar to old mice (Mean: 7519 ± 389) in reference memory place trials. LPS treated young (average proximity (cm): 40 ± 1.4) performed similar 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 reversals, working memory, or cued trials. The average swim speed for reference memory and cued trials showed that the LPS treated were the fastest swimmers, presenting that any deficits were not due to poor motor ability. Stimulating inflammation in a young brain produced only some of the memory deficits seen in aging.
Supported by NIH grant AG016322 to K.R.M.