PMID- 29775613
OWN - NLM
STAT- MEDLINE
DCOM- 20181009
LR  - 20181009
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 501
IP  - 4
DP  - 2018 Jul 2
TI  - Suppression of NLRP3 inflammasome attenuates stress-induced depression-like 
      behavior in NLGN3-deficient mice.
PG  - 933-940
LID - S0006-291X(18)31142-2 [pii]
LID - 10.1016/j.bbrc.2018.05.085 [doi]
AB  - Depression, regulated by central nervous system (CNS), is a significant 
      inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain 
      functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild 
      type (WT) or NLGN3-knockout (KO) mice was established to explore the role of 
      NLGN3 in regulating depression and to reveal the underlying molecular mechanism. 
      The results indicated that NLGN3-knockout markedly reversed the loss of body 
      weight, the reduction of sucrose consumption, the decrease of immobile time in 
      the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS 
      paradigm. CUMS up-regulated corticosterone (CORT) in serum, and down-regulated 
      serotonin (5-HT), norepinephrine (NE) and brain-derived neurotrophic factor 
      (BDNF) in hippocampus of mice, which were significantly reversed by NLGN3 
      deficiency. The results further demonstrated that NLGN3-knockout improved the 
      degenerative neurons in cortex and hippocampus of CUMS-treated mice, accompanied 
      with a significant decrease of ionized calciumbinding adapter molecule 1 (Iba-1) 
      and glial fibrillary acidic protein (GFAP) expressions. Additionally, NLGN3-KO 
      mice challenged with CUMS showed a significant reduction of pro-inflammatory 
      cytokines and chemokine, including tumor necrosis factor-alpha (TNF-alpha), 
      interleukin-18 (IL-18), interleukin-1 beta (IL-1beta), interleukin-4 (IL-4), 
      CC-chemokine ligand-1 (CCL-1) and CXC-chemokine ligand-1 (CXCL-1), in cortex, 
      hippocampus and amygdala tissue samples. Western blot analysis suggested that 
      NLGN3-knockout inhibited the activation of nod-like receptor protein 3 (NLRP3) 
      inflammasome and its adaptor of apoptosis-associated speck like protein (ASC), 
      and reduced the expression of Caspase-1, along with the inactivation of nuclear 
      factor-kappaB (NF-kappaB) in CUMS-challenged mice. The role of NLGN3 in regulating 
      depression in mice was confirmed in vitro using astrocytes stimulated by LPS that 
      NLGN3 knockdown reduced LPS-induced inflammation. Importantly, the suppressive 
      effects of NLGN3-knockdown on inflammatory response were reversed by NLRP3 or ASC 
      over-expression in AST exposed to LPS. In sum, our findings indicated that 
      suppressing NLGN3 played a potential antidepressant role in CUMS animal model by 
      inactivating NLRP3 inflammasome, providing a new therapeutic avenue for 
      depression.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Li, Ze-Qun
AU  - Li ZQ
AD  - Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, 325000, China. Electronic address: zequnli@163.com.
FAU - Yan, Zhi-Yuan
AU  - Yan ZY
AD  - Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, 325000, China.
FAU - Lan, Fu-Jun
AU  - Lan FJ
AD  - Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, 325000, China.
FAU - Dong, Yi-Qun
AU  - Dong YQ
AD  - Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, 325000, China.
FAU - Xiong, Ye
AU  - Xiong Y
AD  - Department of Neurosurgery, First Affiliated Hospital, Wenzhou Medical 
      University, Wenzhou, 325000, China.
LA  - eng
PT  - Journal Article
DEP - 20180521
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
SB  - IM
MH  - Amygdala/metabolism
MH  - Animals
MH  - Astrocytes/metabolism/pathology
MH  - *Behavior, Animal
MH  - Cerebral Cortex/metabolism
MH  - Depression/*etiology/*metabolism
MH  - Gene Deletion
MH  - Gene Knockdown Techniques
MH  - Hippocampus/metabolism
MH  - Inflammasomes/*metabolism
MH  - Lipopolysaccharides
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*deficiency/*metabolism
MH  - Neuroglia/metabolism/pathology
MH  - Neurons/metabolism/pathology
MH  - Phenotype
MH  - Stress, Psychological/*complications
OTO - NOTNLM
OT  - CUMS
OT  - Depression
OT  - NF-kappaB
OT  - NLGN3
OT  - NLRP3 inflammasome
EDAT- 2018/05/19 06:00
MHDA- 2018/10/10 06:00
CRDT- 2018/05/19 06:00
PHST- 2018/05/04 00:00 [received]
PHST- 2018/05/14 00:00 [accepted]
PHST- 2018/05/19 06:00 [pubmed]
PHST- 2018/10/10 06:00 [medline]
PHST- 2018/05/19 06:00 [entrez]
AID - S0006-291X(18)31142-2 [pii]
AID - 10.1016/j.bbrc.2018.05.085 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Jul 2;501(4):933-940. doi: 
      10.1016/j.bbrc.2018.05.085. Epub 2018 May 21.