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Lipopolysaccharide ...
Lipopolysaccharide Increases Cortical Kynurenic Acid and Deficits in Reference Memory in Mice
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Peyton, L (author)
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Oliveros, A (author)
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- Tufvesson-Alm, M (author)
- Karolinska Institutet
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- Schwieler, L (author)
- Karolinska Institutet
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Starski, P (author)
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- Engberg, G (author)
- Karolinska Institutet
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- Erhardt, S (author)
- Karolinska Institutet
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Choi, DS (author)
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(creator_code:org_t)
- 2019-12-17
- 2019
- English.
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In: International journal of tryptophan research : IJTR. - : SAGE Publications. - 1178-6469. ; 12, s. 1178646919891169-
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https://journals.sag...
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http://kipublication...
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https://doi.org/10.1...
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Abstract
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- 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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- ref (subject category)
- art (subject category)
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