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 language | English (US) |
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Pages (from-to) | 1-9 |
Number of pages | 9 |
Journal | Journal of neuroimmunology |
Volume | 313 |
DOIs | |
State | Published - 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