PMID- 29221855
OWN - NLM
STAT- MEDLINE
DCOM- 20190423
LR  - 20190423
IS  - 1090-2139 (Electronic)
IS  - 0889-1591 (Linking)
VI  - 69
DP  - 2018 Mar
TI  - Toll-like receptor-4 regulates anxiety-like behavior and DARPP-32 
      phosphorylation.
PG  - 273-282
LID - S0889-1591(17)30523-8 [pii]
LID - 10.1016/j.bbi.2017.11.022 [doi]
AB  - Toll-like receptors (TLRs) play a crucial role in early innate immune responses 
      to inflammatory agents and pathogens. In the brain, some members of the TLR 
      family are expressed in glial cells and neurons. In particular, TLR4 has been 
      involved in learning and memory processes, stress-induced adaptations, and 
      pathogenesis of neurodegenerative disorders. However, the role of TLR4 in 
      emotional behaviors and their underlying mechanisms are poorly understood. In 
      this study, we investigated the role of TLR4 in emotional and social behavior by 
      using different behavioral approaches, and assessed potential molecular 
      alterations in important brain areas involved in emotional responses. TLR4 
      knockout (KO) mice displayed increased anxiety-like behavior and reduced social 
      interaction compared to wild type control mice. This behavioral phenotype was 
      associated with an altered expression of genes known to be involved in emotional 
      behavior [e.g., brain-derived neurotrophic factor (BDNF) and metabotropic 
      glutamate receptors (mGluRs)]. Interestingly, the mRNA expression of dopamine- 
      and cAMP-regulated phosphoprotein-32 (DARPP-32) was strongly upregulated in 
      emotion-related regions of the brain in TLR4 KO mice. In addition, the 
      phosphorylation levels at Thr75 and Ser97 in DARPP-32 were increased in the 
      frontal cortex of TLR4 KO male mice. These findings indicate that TLR4 signaling 
      is involved in emotional regulation through modulation of DARPP-32, which is a 
      signaling hub that plays a critical role in the integration of numerous 
      neurotransmitter systems, including dopamine and glutamate.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Femenia, T
AU  - Femenia T
AD  - Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. 
      Electronic address: teresa.femenia.canto@ki.se.
FAU - Qian, Y
AU  - Qian Y
AD  - Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
FAU - Arentsen, T
AU  - Arentsen T
AD  - Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
FAU - Forssberg, H
AU  - Forssberg H
AD  - Department of Women's and Children's Health, Karolinska Institutet, 171 76 
      Stockholm, Sweden.
FAU - Diaz Heijtz, R
AU  - Diaz Heijtz R
AD  - Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171206
PL  - Netherlands
TA  - Brain Behav Immun
JT  - Brain, behavior, and immunity
JID - 8800478
RN  - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Anxiety/genetics/*metabolism
MH  - Behavior, Animal/physiology
MH  - Brain/metabolism
MH  - Dopamine and cAMP-Regulated Phosphoprotein 32/*metabolism
MH  - Emotions/*physiology
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/metabolism
MH  - Phosphorylation
MH  - Signal Transduction/*physiology
MH  - Social Behavior
MH  - Toll-Like Receptor 4/genetics/*metabolism
OTO - NOTNLM
OT  - Anxiety
OT  - DARPP-32
OT  - Emotion
OT  - TLR4
OT  - mGluRs
EDAT- 2017/12/10 06:00
MHDA- 2019/04/24 06:00
CRDT- 2017/12/10 06:00
PHST- 2017/06/30 00:00 [received]
PHST- 2017/11/30 00:00 [revised]
PHST- 2017/11/30 00:00 [accepted]
PHST- 2017/12/10 06:00 [pubmed]
PHST- 2019/04/24 06:00 [medline]
PHST- 2017/12/10 06:00 [entrez]
AID - S0889-1591(17)30523-8 [pii]
AID - 10.1016/j.bbi.2017.11.022 [doi]
PST - ppublish
SO  - Brain Behav Immun. 2018 Mar;69:273-282. doi: 10.1016/j.bbi.2017.11.022. Epub 2017 
      Dec 6.