3.8 Article

Lipopolysaccharide Increases Cortical Kynurenic Acid and Deficits in Reference Memory in Mice

期刊

出版社

SAGE PUBLICATIONS LTD
DOI: 10.1177/1178646919891169

关键词

Kynurenic-acid; reference memory; spatial memory; medial-prefrontal cortex; lipopolysaccharide

资金

  1. Mayo-KI Collaborative Travel Award
  2. Mayo Metabolomics Core Pilot Grant
  3. Samuel C. Johnson Genomics of Addiction Program at Mayo Clinic
  4. Ulm Foundation
  5. Swedish Medical Research Council [SE: 2017-00875]
  6. Swedish Brain Foundation
  7. Marta Lundqvists Stiftelse
  8. Petrus och Augusta Hedlunds Stiftelse
  9. Torsten Soderbergs Stiftelse
  10. NIH T32 Predoctoral Training Grant [GM072474]

向作者/读者索取更多资源

Kynurenic acid (KYNA), a glial-derived metabolite of tryptophan metabolism, is an antagonist of the alpha 7 nicotinic acetylcholine receptor and the glycine-binding site of N-methyl-d-aspartate (NMDA) receptors. Kynurenic acid levels are increased in both the brain and cerebrospinal fluid of several psychiatric disorders including bipolar disorder, schizophrenia, and Alzheimer disease. In addition, pro-inflammatory cytokines have been found to be elevated in the blood of schizophrenic patients suggesting inflammation may play a role in psychiatric illness. As both pro-inflammatory cytokines and KYNA can be elevated in the brain by peripheral lipopolysaccharide (LPS) injection, we therefore sought to characterize the role of neuroinflammation on learning and memory using a well-described dual-LPS injection model. Mice were injected with an initial injection (0.25 mg/kg LPS, 0.50 mg/kg, or saline) of LPS and then administrated a second injection 16 hours later. Our results indicate both 0.25 and 0.50 mg/kg dual-LPS treatment increased l-kynurenine and KYNA levels in the medial pre-frontal cortex (mPFC). Mice exhibited impaired acquisition of CS+ (conditioned stimulus) Pavlovian conditioning. Notably, mice showed impairment in reference memory while working memory was normal in an 8-arm maze. Taken together, our findings suggest that neuroinflammation induced by peripheral LPS administration contributes to cognitive dysfunction.

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