hUC-MSCs ameliorated CUMS-induced depression by modulating complement C3 signaling-mediated microglial polarization during astrocyte-microglia crosstalk

Li, Jing; Wang, Hualong; Du, Chongbo; Jin, Xiaojing; Geng, Yichao; Han, Bing; Ma, Qing; Li, Quanhai; Wang, Qian; Guo, Yidi; Wang, Mingwei; Yan, Bowei

doi:10.1016/j.brainresbull.2020.07.004

Cited by 30 publications

(26 citation statements)

References 39 publications

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“…As shown in Figure 1 . The neurotoxic effect of complement component 3 (C3), a strong marker of A1 astrocytes, has been confirmed in a variety of CNS diseases, especially the interaction between the C3 cleavage fragment, C3a, and its receptor, C3aR, on neurons (Guo et al, 2010 ; Lian et al, 2015 ; Li J. et al, 2020 ; Yadav et al, 2021 ). However, the A1 and A2 phenotypes were not proposed to be universal or all-encompassing, they were widely misinterpreted as evidence for a binary polarization of reactive astrocytes in either neurotoxic or neuroprotective states, which could be readily identified in any CNS disease, acute or chronic, like the once-popular, but now discarded, Th1–Th2 lymphocyte and M1–M2 microglia polarization theories.…”

Section: Introductionmentioning

confidence: 99%

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Zhang

Ning

2021

Front. Cell. Neurosci.

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Traumatic central nervous system (CNS) injury, which includes both traumatic brain injury (TBI) and spinal cord injury (SCI), is associated with irreversible loss of neurological function and high medical care costs. Currently, no effective treatment exists to improve the prognosis of patients. Astrocytes comprise the largest population of glial cells in the CNS and, with the advancements in the field of neurology, are increasingly recognized as having key functions in both the brain and the spinal cord. When stimulated by disease or injury, astrocytes become activated and undergo a series of changes, including alterations in gene expression, hypertrophy, the loss of inherent functions, and the acquisition of new ones. Studies have shown that astrocytes are highly heterogeneous with respect to their gene expression profiles, and this heterogeneity accounts for their observed context-dependent phenotypic diversity. In the inured CNS, activated astrocytes play a dual role both as regulators of neuroinflammation and in scar formation. Identifying the subpopulations of reactive astrocytes that exert beneficial or harmful effects will aid in deciphering the pathological mechanisms underlying CNS injuries and ultimately provide a theoretical basis for the development of effective strategies for the treatment of associated conditions. Following CNS injury, as the disease progresses, astrocyte phenotypes undergo continuous changes. Although current research methods do not allow a comprehensive and accurate classification of astrocyte subpopulations in complex pathological contexts, they can nonetheless aid in understanding the roles of astrocytes in disease. In this review, after a brief introduction to the pathology of CNS injury, we summarize current knowledge regarding astrocyte activation following CNS injury, including: (a) the regulatory factors involved in this process; (b) the functions of different astrocyte subgroups based on the existing classification of astrocytes; and (c) attempts at astrocyte-targeted therapy.

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Section: Introductionmentioning

confidence: 99%

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Zhang

Ning

2021

Front. Cell. Neurosci.

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“…In recent years, the over-accumulation of pro-inflammatory cytokines in the blood and brain tissues has been widely-reported to be associated with the pathogenesis of depression. For example, the over-activation of microglia has been repeatedly reported to mediate the progression of depression in rodent animals ( Zhao et al, 2016 ; Duan et al, 2020 ; Jing Li et al, 2020 ; Wu et al, 2020 ; Kumar et al, 2021 ), and suppression of neuroinflammation by minocycline treatment could can ameliorate depressive symptoms ( Wang et al, 2020 ; Bassett et al, 2021 ). Individuals suffering from depression have increased levels of pro-inflammatory cytokines in the blood ( Petralia et al, 2020 ; Primo de Carvalho Alves and Sica da Rocha, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…It is known that the development of neuroinflammatory responses at stress conditions is usually accompanied with significant reductions in anti-inflammatory mediators ( Zhao et al, 2016 ; Duan et al, 2020 ; Jing Li et al, 2020 ; Wu et al, 2020 ; Kumar et al, 2021 ). Thus, enhancing the production of anti-inflammatory mediators in the brain may mediate the antidepressant effect of I3C.…”

Section: Discussionmentioning

confidence: 99%

“…In rodent models of depression and anxiety, high levels of pro-inflammatory cytokines and low levels of anti-inflammatory mediators such as IL-10 and IL-4 in the brain are also correlated with the progression of abnormal behaviors ( Wang et al, 2018 ; Walker et al, 2019 ; Zhang et al, 2019 ; Guha et al, 2020 ; Wu et al, 2021 ). Skewing the neuroinflammatory responses in the brain towards an anti-inflammatory state can prevent the progression of abnormal behaviors in animals stimulated with detrimental stress ( Zhao et al, 2016 ; Duan et al, 2020 ; Jing Li et al, 2020 ; Wu et al, 2020 ; Kumar et al, 2021 ). Moreover, direct infusion of pro-inflammatory cytokines such as IL-1β and interferon-α (INF-α) into the brain in animals can also induce behavioral abnormalities ( Park et al, 2015 ; Zhifei Li et al, 2020 ), and clinically-available antidepressants such as fluoxetine can improve behaviors in depressed animals ( Du et al, 2016 ) and patients suffering from generalized anxiety disorders ( Hou et al, 2019 ) partially through suppression of inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Indole-3-Carbinol Selectively Prevents Chronic Stress-Induced Depression-but not Anxiety-Like Behaviors via Suppressing Pro-Inflammatory Cytokine Production and Oxido-Nitrosative Stress in the Brain

Pan

Yang

et al. 2022

Front. Pharmacol.

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Indole-3-carbinol (I3C), a phytochemical enriched in most cruciferous vegetables, has been shown to display various biological activities such as anti-oxidative stress, anti-inflammation, and anti-carcinogenesis. In this study, we investigated the regulatory effect of I3C on chronic stress-induced behavioral abnormalities in mice. Results showed that repeated I3C treatment at the dose of 10, 30, and 60 mg/kg prevented chronic social defeat stress (CSDS)-induced behavioral abnormalities in the tail suspension test, forced swimming test, sucrose preference test, and social interaction test in mice, and did not affect CSDS-induced behavioral abnormalities in the elevated plus maze, light-dark test, and open-field test, suggesting that the I3C treatment selectively prevents the onset of depression- but not anxiety-like behaviors in chronically stressed mice. Further analysis demonstrated that repeated I3C treatment (60 mg/kg, 10 days) prevented CSDS-induced increases in levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) mRNA and protein, but did not affect CSDS-induced decreases in levels of IL-4, IL-10, and Ym-1 mRNA and/or protein in the hippocampus and prefrontal cortex, suggesting that I3C can selectively prevent chronic stress-induced pro-inflammatory but not anti-inflammatory responses in the brain. Further analysis showed that repeated I3C treatment (60 mg/kg, 10 days) prevented CSDS-induced increases in levels of nitrite and malondialdehyde (MDA), decreases in contents of glutathione (GSH), and decreases in levels of brain derived neurotrophic factor (BDNF) protein in the hippocampus and prefrontal cortex. These results demonstrated that I3C selectively prevents chronic stress-induced depression-like behaviors in mice likely through suppressing neuroinflammation and oxido-nitrosative stress in the brain.

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“…Additionally, some inflammatory factors, such as CRP, IL-6, and TNF-α, can be used as biomarkers of depression [121]. Microglia and astrocytes are also found to be activated in the brain of depressed mice [122]. Therefore, neuroinflammation may be the key pathogenesis of depressive disorder.…”

Section: Neuroinflammation Reactionmentioning

confidence: 99%

"Natural Compounds and Depressive Disorder: A Review Highlighting Botanical Sources and Reaction Mechanisms"

Wang

2021

BJSTR

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Depressive disorder is a typical mental illness characterized by depressed mood and anhedonia, with a great burden to patients and society. Currently, only a small minority of medicines are efficient in the clinic with high prices and various adverse reactions, including sleep disorders and gastrointestinal reactions. To develop new antidepressants, pharmacists have gradually turned their attention to phytochemicals, especially those from traditional Chinese medicine (TCM). Natural products could be good candidates for developing effective drugs and valid therapeutic strategies. In this article, we reviewed more than 20 natural compounds from TCMs with protective action against the depressive disorder, and their reaction mechanisms were reviewed from four aspects: reversing neurotransmitter imbalance, maintaining neuroendocrine homeostasis, alleviating synaptic plasticity dysfunction, and inhibiting neuroinflammation.

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hUC-MSCs ameliorated CUMS-induced depression by modulating complement C3 signaling-mediated microglial polarization during astrocyte-microglia crosstalk

Cited by 30 publications

References 39 publications

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Reactive Astrocytes in Central Nervous System Injury: Subgroup and Potential Therapy

Indole-3-Carbinol Selectively Prevents Chronic Stress-Induced Depression-but not Anxiety-Like Behaviors via Suppressing Pro-Inflammatory Cytokine Production and Oxido-Nitrosative Stress in the Brain

"Natural Compounds and Depressive Disorder: A Review Highlighting Botanical Sources and Reaction Mechanisms"

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