PMID- 33161108
OWN - NLM
STAT- MEDLINE
DCOM- 20210504
LR  - 20240226
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 741
DP  - 2021 Jan 10
TI  - Protection of hUC-MSCs against neuronal complement C3a receptor-mediated NLRP3 
      activation in CUMS-induced mice.
PG  - 135485
LID - S0304-3940(20)30755-2 [pii]
LID - 10.1016/j.neulet.2020.135485 [doi]
AB  - BACKGROUND: Hyperactivation of complement C3 and inflammation-related activation 
      of NLR family pyrin domain containing 3 (NLRP3) inflammasome are implicated in 
      the etiology of stress-related disorders. Studies have shown that human umbilical 
      cord mesenchymal stromal cells (hUC-MSCs) have immunomodulatory and 
      anti-inflammatory effects; however, the mechanism remains unclear. METHODS: 
      hUC-MSCs were administered to chronic unpredictable mild stress (CUMS) model mice 
      once a week for four weeks. After the administration of hUC-MSCs, several 
      parameters were assessed, including behavioral performance, synapse-related 
      proteins, complement C3 receptors (C3aR) in neurons, and the NLRP3 inflammasome. 
      Then, CUMS mice were injected with SB290157, a complement C3aR antagonist, and 
      the behavioral index and NLRP3 inflammasome activation were tested. RESULTS: The 
      open-field and forced swimming behavioral tests showed an improvement in 
      depression-like behaviors in the CUMS-exposed mice after the administration of 
      hUC-MSCs. Treatment with hUC-MSCs significantly decreased the neuronal C3aR 
      levels and alleviated synaptic damage. Furthermore, the levels of the NLRP3 
      inflammasome and inflammatory factors were reduced after hUC-MSC administration. 
      In particular, treatment with a C3aR antagonist also decreased NLRP3 inflammasome 
      expression and inflammation, which was consistent with the observed improvements 
      after hUC-MSC treatment. CONCLUSION: hUC-MSCs can attenuate NLRP3 activation in 
      CUMS-induced mice, which may be correlated with C3aR in neurons.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Li, Jing
AU  - Li J
AD  - Department of Neurology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China; Brain Aging and Cognitive Neuroscience Key Laboratory 
      of Hebei Province, Shijiazhuang, Hebei, China.
FAU - Tian, Shujuan
AU  - Tian S
AD  - Department of Neurology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China; Brain Aging and Cognitive Neuroscience Key Laboratory 
      of Hebei Province, Shijiazhuang, Hebei, China. Electronic address: 
      jtian72@126.com.
FAU - Wang, Hualong
AU  - Wang H
AD  - Department of Neurology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China; Brain Aging and Cognitive Neuroscience Key Laboratory 
      of Hebei Province, Shijiazhuang, Hebei, China.
FAU - Wang, Yanyong
AU  - Wang Y
AD  - Department of Neurology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China; Brain Aging and Cognitive Neuroscience Key Laboratory 
      of Hebei Province, Shijiazhuang, Hebei, China.
FAU - Du, Chongbo
AU  - Du C
AD  - Department of Neurology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China; Brain Aging and Cognitive Neuroscience Key Laboratory 
      of Hebei Province, Shijiazhuang, Hebei, China.
FAU - Fang, Jiyu
AU  - Fang J
AD  - Department of Neurology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China; Brain Aging and Cognitive Neuroscience Key Laboratory 
      of Hebei Province, Shijiazhuang, Hebei, China.
FAU - Wang, Xiaoxiao
AU  - Wang X
AD  - Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, 
      China.
FAU - Wang, Yufeng
AU  - Wang Y
AD  - Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, China.
FAU - Gong, Zhexuan
AU  - Gong Z
AD  - Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, China.
FAU - Yan, Baoyong
AU  - Yan B
AD  - Cell Therapy Laboratory, The First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China. Electronic address: yanby7001@163.com.
FAU - Wang, Mingwei
AU  - Wang M
AD  - Department of Neurology, the First Hospital of Hebei Medical University, 
      Shijiazhuang, Hebei, China; Brain Aging and Cognitive Neuroscience Key Laboratory 
      of Hebei Province, Shijiazhuang, Hebei, China. Electronic address: 
      mingweiwang88@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201105
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Complement C3)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-2)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - PL21OR4LXE (lorukafusp alfa)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal
MH  - Behavior, Animal
MH  - Complement C3/*metabolism
MH  - Disease Models, Animal
MH  - Hippocampus/metabolism
MH  - Inflammasomes/metabolism
MH  - Interleukin-2
MH  - Male
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice, Inbred ICR
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Neuronal Plasticity
MH  - Stress, Psychological/*metabolism
MH  - Umbilical Cord/cytology
MH  - Mice
OTO - NOTNLM
OT  - Chronic unpredictable mild stress
OT  - Complement C3a receptor
OT  - Human umbilical cord mesenchymal stromal cells
OT  - NLRP3 inflammasome
EDAT- 2020/11/09 06:00
MHDA- 2021/05/05 06:00
CRDT- 2020/11/08 20:28
PHST- 2020/05/12 00:00 [received]
PHST- 2020/09/21 00:00 [revised]
PHST- 2020/11/01 00:00 [accepted]
PHST- 2020/11/09 06:00 [pubmed]
PHST- 2021/05/05 06:00 [medline]
PHST- 2020/11/08 20:28 [entrez]
AID - S0304-3940(20)30755-2 [pii]
AID - 10.1016/j.neulet.2020.135485 [doi]
PST - ppublish
SO  - Neurosci Lett. 2021 Jan 10;741:135485. doi: 10.1016/j.neulet.2020.135485. Epub 
      2020 Nov 5.