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

Abstract

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.

• Authors: Lee Peyton, Alfredo Oliveros, Maximilian Tufvesson-Alm, Lilly Schwieler, Phillip Starski, Göran Engberg, Sopie Erhardt, Doo-Sup Choi
• Journal: International journal of tryptophan research : IJTR (Int J Tryptophan Res) Vol. 12 Pg. 1178646919891169 ( 2019) ISSN: 1178-6469 [Print] United States
• PMID: 31896932 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2019.