LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning

A. Oliveros, K. Wininger, J. Sens, M. K. Larsson, X. C. Liu, S. Choi, A. Faka, L. Schwieler, G. Engberg, S. Erhardt, D. S. Choi

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The N-Methyl-D-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT). Our results also indicate that dual-LPS increases Nrgn phosphorylation and concomitantly reduces phosphorylation of calmodulin kinase-II (CaMKII). We confirmed that systemic blockade of kynurenine-3 monooxygenase in conjunction with kynurenine administration results in significant increases in Nrgn phosphorylation and a significant reduction of CaMKII phosphorylation in the mPFC. Consequently, dual-LPS administration induced significant impairments in stimulus processing during Pavlovian conditioning. Taken together, our study indicates that elevations in KYNA in the mPFC can directly regulate NMDA-Nrgn-CaMKII signaling, suggesting that neuroinflammatory conditions affecting this pathway may be associated with cognitive dysfunction.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalJournal of neuroimmunology
Volume313
DOIs
StatePublished - Dec 15 2017

Keywords

  • Kynurenic-acid
  • Lipopolysaccharide
  • Medial-prefrontal cortex
  • NFAT
  • Neurogranin
  • Ventral-hippocampus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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