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

Autor: 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
Rok vydání: 2017
Předmět:
Lipopolysaccharides
Male
0301 basic medicine
medicine.medical_specialty
Calmodulin
Conditioning
Classical
Immunology
Prefrontal Cortex
Kynurenic Acid
Hippocampus
Receptors
N-Methyl-D-Aspartate
Article
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Kynurenic acid
Ca2+/calmodulin-dependent protein kinase
Internal medicine
medicine
Animals
Immunology and Allergy
Neurogranin
Analysis of Variance
NFATC Transcription Factors
biology
Prepulse Inhibition
NFAT
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
nervous system
Neurology
chemistry
Rotarod Performance Test
biology.protein
Phosphorylation
NMDA receptor
Neurology (clinical)
Calcium-Calmodulin-Dependent Protein Kinase Type 2
030217 neurology & neurosurgery
Kynurenine
Signal Transduction
Synaptosomes
Zdroj: Journal of Neuroimmunology. 313:1-9
ISSN: 0165-5728
Popis: 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-I I (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.
Databáze: OpenAIRE
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