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      Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system.

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          Abstract

          Acute cognitive impairment (i.e., delirium) is common in elderly emergency department patients and frequently results from infections that are unrelated to the central nervous system. Since activation of the peripheral innate immune system induces brain microglia to produce inflammatory cytokines that are responsible for behavioral deficits, we investigated if aging exacerbated neuroinflammation and sickness behavior after peripheral injection of lipopolysaccharide (LPS). Microarray analysis revealed a transcriptional profile indicating the presence of primed or activated microglia and increased inflammation in the aged brain. Furthermore, aged mice had a unique gene expression profile in the brain after an intraperitoneal injection of LPS, and the LPS-induced elevation in the brain inflammatory cytokines and oxidative stress was both exaggerated and prolonged compared with adults. Aged mice were anorectic longer and lost more weight than adults after peripheral LPS administration. Moreover, reductions in both locomotor and social behavior remained 24 h later in aged mice, when adults had fully recovered, and the exaggerated neuroinflammatory response in aged mice was not reliably paralleled by increased circulating cytokines in the periphery. Taken together, these data establish that activation of the peripheral innate immune system leads to exacerbated neuroinflammation in the aged as compared with adult mice. This dysregulated link between the peripheral and central innate immune system is likely to be involved in the severe behavioral deficits that frequently occur in older adults with systemic infections.

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          Author and article information

          Journal
          FASEB J
          FASEB journal : official publication of the Federation of American Societies for Experimental Biology
          Wiley
          1530-6860
          0892-6638
          Aug 2005
          : 19
          : 10
          Affiliations
          [1 ] Division of Nutritional Sciences, University of Illinois, Urbana, Illinois 61801, USA.
          Article
          05-3776fje
          10.1096/fj.05-3776fje
          15919760
          1df896ec-6589-438d-9b9d-076d18e0cbc8

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