PMID- 29153599
OWN - NLM
STAT- MEDLINE
DCOM- 20171129
LR  - 20190127
IS  - 1872-8421 (Electronic)
IS  - 0165-5728 (Print)
IS  - 0165-5728 (Linking)
VI  - 313
DP  - 2017 Dec 15
TI  - LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated 
      with deficits in stimulus processing during Pavlovian conditioning.
PG  - 1-9
LID - S0165-5728(16)30465-9 [pii]
LID - 10.1016/j.jneuroim.2017.09.010 [doi]
AB  - 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 (NFkappaB) 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.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Oliveros, A
AU  - Oliveros A
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic 
      College of Medicine, Rochester, MN 55905, USA.
FAU - Wininger, K
AU  - Wininger K
AD  - Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 
      55905, USA.
FAU - Sens, J
AU  - Sens J
AD  - Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 
      55905, USA.
FAU - Larsson, M K
AU  - Larsson MK
AD  - Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, 
      Sweden.
FAU - Liu, X C
AU  - Liu XC
AD  - Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, 
      Sweden.
FAU - Choi, S
AU  - Choi S
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic 
      College of Medicine, Rochester, MN 55905, USA.
FAU - Faka, A
AU  - Faka A
AD  - Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, 
      Sweden.
FAU - Schwieler, L
AU  - Schwieler L
AD  - Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, 
      Sweden.
FAU - Engberg, G
AU  - Engberg G
AD  - Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, 
      Sweden.
FAU - Erhardt, S
AU  - Erhardt S
AD  - Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, 
      Sweden.
FAU - Choi, D S
AU  - Choi DS
AD  - Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic 
      College of Medicine, Rochester, MN 55905, USA; Department of Psychiatry and 
      Psychology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA; 
      Neurobiology of Disease Program, Mayo Clinic College of Medicine, Rochester, MN 
      55905, USA. Electronic address: choids@mayo.edu.
LA  - eng
GR  - R01 AA018779/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170928
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NFATC Transcription Factors)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 132654-77-4 (Neurogranin)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - H030S2S85J (Kynurenic Acid)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
MH  - Conditioning, Classical
MH  - Hippocampus/drug effects/metabolism
MH  - Kynurenic Acid/*metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NFATC Transcription Factors/metabolism
MH  - Neurogranin/*metabolism
MH  - Prefrontal Cortex/*drug effects
MH  - Prepulse Inhibition/drug effects
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Rotarod Performance Test
MH  - Signal Transduction/*drug effects
MH  - Synaptosomes/drug effects
PMC - PMC5728408
MID - NIHMS912907
OTO - NOTNLM
OT  - Kynurenic-acid
OT  - Lipopolysaccharide
OT  - Medial-prefrontal cortex
OT  - NFAT
OT  - Neurogranin
OT  - Ventral-hippocampus
EDAT- 2017/11/21 06:00
MHDA- 2017/12/01 06:00
PMCR- 2018/12/15
CRDT- 2017/11/21 06:00
PHST- 2016/12/15 00:00 [received]
PHST- 2017/05/04 00:00 [revised]
PHST- 2017/09/27 00:00 [accepted]
PHST- 2017/11/21 06:00 [entrez]
PHST- 2017/11/21 06:00 [pubmed]
PHST- 2017/12/01 06:00 [medline]
PHST- 2018/12/15 00:00 [pmc-release]
AID - S0165-5728(16)30465-9 [pii]
AID - 10.1016/j.jneuroim.2017.09.010 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2017 Dec 15;313:1-9. doi: 10.1016/j.jneuroim.2017.09.010. Epub 
      2017 Sep 28.