PMID- 32681971 OWN - NLM STAT- MEDLINE DCOM- 20210929 LR - 20210929 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 163 DP - 2020 Oct TI - hUC-MSCs ameliorated CUMS-induced depression by modulating complement C3 signaling-mediated microglial polarization during astrocyte-microglia crosstalk. PG - 109-119 LID - S0361-9230(20)30551-7 [pii] LID - 10.1016/j.brainresbull.2020.07.004 [doi] AB - BACKGROUND: Major depressive disorder (MDD) has been shown to be related to immune inflammation and the complement system. Previous studies have suggested that human umbilical cord mesenchymal stem cells (hUC-MSCs) play an important role in inflammatory diseases. METHODS: hUC-MSCs were administered into chronic unpredictable mild stress model (CUMS) mice through the tail vein once a week for 4 weeks. After the administration of hUC-MSCs, the depression-like and anxiety-like phenotypes, neuronal histopathology, synaptic-related protein expression and inflammatory index of the mice were assessed. Microglial M1/M2 polarization and the expression of C3a in astrocytes and C3aR in microglia was detected by immunofluorescence co-localization. Then, CUMS mice were injected with a C3aR antagonist, and the expression of C3a and C3aR and microglial polarization were observed. RESULTS: Based on the sucrose preference and tail suspension tests, hUC-MSCs ameliorated the depression-like behaviors of CUMS mice. Additionally, the anxiety-like behaviors of CUMS mice in the open-field and plus-maze tests were improved after the administration of hUC-MSCs. hUC-MSCs altered microglia polarization by alleviating complement C3a-C3aR signaling activation, which decreased pro-inflammatory factor levels and increased anti-inflammatory factor levels, alleviating neuronal damage and synaptic deficits. CONCLUSION: hUC-MSCs have therapeutic effects on anxiety-like and depressive-like phenotypes caused by CUMS. They can alter the polarization of microglia by inhibiting C3a-C3aR signaling to reduce neuroinflammation. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Li, Jing AU - Li J AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. FAU - Wang, Hualong AU - Wang H AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. FAU - Du, Chongbo AU - Du C AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. FAU - Jin, Xiaojing AU - Jin X AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. FAU - Geng, Yuan AU - Geng Y AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. FAU - Han, Bing AU - Han B AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. FAU - Ma, Qinying AU - Ma Q AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. FAU - Li, Quanhai AU - Li Q AD - Cell Therapy Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, China; Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, 050017, China. FAU - Wang, Qian AU - Wang Q AD - Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, 050017, China. FAU - Guo, Yidi AU - Guo Y AD - Basic Medical College, Hebei Medical University, Shijiazhuang, Hebei, 050017, China. FAU - Wang, Mingwei AU - Wang M AD - Department of Neurology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Brain Aging and Cognitive Neuroscience Key Laboratory of Hebei Province, Shijiazhuang, Hebei 050017, China. Electronic address: mingweiwang88@163.com. FAU - Yan, Baoyong AU - Yan B AD - Cell Therapy Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050031, China. Electronic address: yanby7001@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200715 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (C3 protein, mouse) RN - 0 (Complement C3) SB - IM MH - Animals MH - Astrocytes/*metabolism MH - Chronic Disease MH - Complement C3/antagonists & inhibitors/*metabolism MH - Depressive Disorder, Major/*metabolism/psychology/therapy MH - Humans MH - Male MH - Maze Learning/physiology MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mice MH - Mice, Inbred ICR MH - Microglia/*metabolism MH - Stress, Psychological/*metabolism/psychology/therapy MH - Umbilical Cord/cytology/*transplantation OTO - NOTNLM OT - Complement C3 OT - Microglial polarization OT - Neuroinflammation OT - hUC-MSCs EDAT- 2020/07/19 06:00 MHDA- 2021/09/30 06:00 CRDT- 2020/07/19 06:00 PHST- 2020/03/10 00:00 [received] PHST- 2020/06/18 00:00 [revised] PHST- 2020/07/08 00:00 [accepted] PHST- 2020/07/19 06:00 [pubmed] PHST- 2021/09/30 06:00 [medline] PHST- 2020/07/19 06:00 [entrez] AID - S0361-9230(20)30551-7 [pii] AID - 10.1016/j.brainresbull.2020.07.004 [doi] PST - ppublish SO - Brain Res Bull. 2020 Oct;163:109-119. doi: 10.1016/j.brainresbull.2020.07.004. Epub 2020 Jul 15.