2.Immunological Markers for Central Nervous System Glia.
Hao HUANG ; Wanjun HE ; Tao TANG ; Mengsheng QIU
Neuroscience Bulletin 2023;39(3):379-392
Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.
Neuroglia/metabolism*
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Central Nervous System
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Oligodendroglia/metabolism*
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Astrocytes/metabolism*
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Microglia
3.The triggering receptor expressed on myeloid cells 2-apolipoprotein E signaling pathway in diseases.
Shukai LYU ; Zhuoqing LAN ; Caixia LI
Chinese Medical Journal 2023;136(11):1291-1299
Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane receptor on myeloid cells and plays an important role in the body's immune defense. Recently, TREM2 has received extensive attention from researchers, and its activity has been found in Alzheimer's disease, neuroinflammation, and traumatic brain injury. The appearance of TREM2 is usually accompanied by changes in apolipoprotein E (ApoE), and there has been a lot of research into their structure, as well as the interaction mode and signal pathways involved in them. As two molecules with broad and important roles in the human body, understanding their correlation may provide therapeutic targets for certain diseases. In this article, we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development. We further discussed the positive or negative effects of the TREM2-ApoE pathway on nervous system immunity and inflammation.
Humans
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Alzheimer Disease/metabolism*
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Apolipoproteins E/genetics*
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Microglia/metabolism*
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Myeloid Cells/metabolism*
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Signal Transduction
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Neuroinflammatory Diseases
5.Role of microglial activation induced by α-synuclein in pathogenesis of Parkinson's disease.
Sen QIAO ; Jian-hong LUO ; Jing-hua JIN
Journal of Zhejiang University. Medical sciences 2012;41(2):210-214
Parkinson's disease (PD), a progressive neurodegenerative disorder, is pathologically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of deposits of aggregated α-synuclein in intracellular inclusions known as Lewy bodies (LB). A highly localized inflammatory response mediated by reactive microglia is prominent in PD brains, but the mechanisms underlying the microglial activation are poorly understood. Recently some lines of evidences have shown that monomeric, or aggregated α-synuclein can activate microglia, the toxic factors released from activated microglia may lead to the cell death of dopaminergic neurons. This review is to summarize the recent progress on the role of α-synuclein induced microglia activation on the PD pathogenesis and progression, and to discuss the possible mechanisms involved.
Humans
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Microglia
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pathology
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Parkinson Disease
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etiology
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metabolism
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pathology
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alpha-Synuclein
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chemistry
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metabolism
;
physiology
6.Role of microglial pyroptosis in hypoxic-ischemic brain damage.
Lan-Lan TAN ; Mei LI ; Chen-Xi FENG ; Li-Xiao XU ; Xin DING ; Bin SUN ; Gen LI ; Xing FENG
Chinese Journal of Contemporary Pediatrics 2020;22(11):1226-1232
OBJECTIVE:
To investigate the role of microglial pyroptosis in hypoxic-ischemic brain damage.
METHODS:
An oxygen-glucose deprivation/reoxygenation (OGD/R) model of rat microglial cells were cultured in vitro. Western blot was used to measure the expression of the pyroptosis-related proteins caspase-1, interleukin-1β (IL-1β), and N-terminal gasdermin D (GSDMD-N) at 0, 1, 3, 6, 12, and 24 hours after OGD/R. After the microglial cells were transfected with lentivirus-mediated silenced gasdermin D (GSDMD), immunofluorescence assay and Western blot were used to measure the transfection rate of GSDMD. Microglial cell lines were divided into three groups: normal control, negative control, and LV-sh_GSDMD (lentivirus-mediated GSDMD silencing). CCK-8 assay and LDH kit were used to observe the effect of GSDMD silencing on the viability and toxicity of microglial cells at 24 hours after OGD/R. Western blot was used to observe the effect of GSDMD silencing on the levels of caspase-1, GSDMD-N, and IL-1β in the microglial cells at 24 hours after OGD/R.
RESULTS:
The expression levels of the pyroptosis-related proteins caspase-1, GSDMD-N, and IL-1β in microglial cells were upregulated since 0 hour after OGD/R and reached the peak levels at 24 hours. A microglial cell model of lentivirus-mediated GSDMD silencing was successfully constructed. At 24 hours after OGD/R, compared with the normal control group, the GSDMD silencing group had a significant increase in the cell viability and a significant reduction in the cytotoxicity (P<0.05), as well as significant reductions in the protein expression levels of caspase-1, GSDMD-N, and IL-1β in microglial cells (P<0.05).
CONCLUSIONS
Lentivirus silencing of the key substrate protein for pyroptosis GSDMD can alleviate hypoxic-ischemic brain damage, suggesting that microglial pyroptosis aggravates hypoxic-ischemic brain damage.
Animals
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Brain/metabolism*
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Intracellular Signaling Peptides and Proteins
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Microglia/metabolism*
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Pyroptosis
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Rats
7.Influence of NF-kappa B on the development and regulation of neural system.
Xi-ping CHEN ; Lu-yang TAO ; Mei DING
Journal of Forensic Medicine 2002;18(2):112-114
Nuclear factor-kappa B (NF-kappa B) plays an important role in controlling infection, immunity responses, cellar differentiation and apoptosis. It is of characteristics especially in neural system. NF-kappa B exist widely in neural cells and transfer from plasma into nucleolus through diversified activation passages. in addition, NF-kappa B is also a key factor in the development of the neural system, anti-apoptosis and modulating the activity of glia cells. It is of great significance in the forensic science.
Apoptosis
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Cell Nucleus/metabolism*
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Forensic Medicine/methods*
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Microglia/physiology*
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NF-kappa B/physiology*
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Neurons/metabolism*
8.Characterization and identification of primarily cultured astrocytes and microglia.
Xiang CHENG ; Yanan GENG ; Yaqun JIANG ; Tong ZHAO ; Lingling ZHU ; Yulin DENG
Chinese Journal of Biotechnology 2023;39(10):4234-4245
The aim of this study was to investigate the growth characteristics of primarily cultured astrocytes and microglia of different generations and then optimize the method for obtaining primary astrocytes and microglia effectively. Primarily cultured microglia were isolated and purified from the cortices of neonatal mice. The proliferation curve of mixed glia cells was measured by Cell Counting Kit-8 (CCK-8) assay, the proportion of astrocytes and microglia was detected by flow cytometry, and the polarization of the two types of glia cells was identified by immunofluorescence staining. Cell growth results showed that the mixed glia cells of P0 and P1 generation had the best proliferative activity; 97.3% of the high purity microglia could be obtained by mechanical shaking at 170 r/min for 30 min, and there was no significant difference in the morphology of ionized calcium-binding adapter molecule 1 (Iba-1) positive microglia and the proportion of M1 and M2 phenotype among the P0, P1 and P2 generations of microglia isolated by the above methods. Moreover, 95.7 % of the high purity astrocytes could be obtained by astrocyte cell surface antigen-2 (ACSA-2) magnetic beads separation, and there was no significant difference in the morphology of glial fibrillary acidic protein (GFAP) positive astrocyte and the proportion of A1 and A2 phenotype among the P0, P1 and P2 generations of astrocyte isolated by the above methods. Taken together, this study observed the growth characteristics of primarily cultured microglia and astrocyte in vitro, and then proved the best generations for purifying microglia and astrocytes. Finally, we optimized the methods of obtaining microglia and astrocyte, and verified that continuous culture within 2 generations will not affect the functional phenotypes of glia cells. These results provide technical support for studying the molecular mechanism of inflammation-associated diseases in nervous system.
Mice
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Animals
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Astrocytes/metabolism*
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Microglia/metabolism*
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Cell Count
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Flow Cytometry/methods*
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Cell Proliferation
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Cells, Cultured
9.Mechanism of stress-induced microglial activation in depression and traditional Chinese medicine regulation.
Yi-Ze SUN ; Hai-Bin ZHAO ; Zhe-Yi WANG
China Journal of Chinese Materia Medica 2023;48(16):4285-4294
Depression exists with high prevalence and heavy disease burden. Stress events play a key role in the occurrence of depression, but the pathological mechanism has not been fully clarified by reason of the complexity and heterogeneity. In recent years, neuroinflammation as a pathological mechanism of depression has received extensive attention. The activated microglia is regarded as the marker of neuroinflammation, which is an important link of stress-induced depression. Stress might induce microglia activation through pattern recognition receptors(PRR), intestinal flora, hypothalamic-pituitary-adrenal(HPA) axis, and other pathways. Cross-talk between impaired microglia function and neurobiological factors such as inflammatory cytokines, serotonin metabolism, and neuroplasticity may lead to depression. At present, a large number of studies have proved that traditional Chinese medicine(TCM) plays an anti-depressive role by inhibiting microglia activation, which may be potential treatment strategies for depressive disorder. This paper reviewed the research progress of stress-induced microglia activation in depression and summarized the mechanism of TCM against depression with regard to microglia, hoping to provide experimental evidence and consideration for TCM against depression through microglia.
Humans
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Cytokines/metabolism*
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Depression/drug therapy*
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Medicine, Chinese Traditional
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Microglia/metabolism*
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Neuroinflammatory Diseases
10.The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities.
Qiyuan ZHUANG ; Hui YANG ; Ying MAO
Neuroscience Bulletin 2023;39(3):393-408
Glioma is the most common and lethal intrinsic primary tumor of the brain. Its controversial origins may contribute to its heterogeneity, creating challenges and difficulties in the development of therapies. Among the components constituting tumors, glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation. Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor, in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation. Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states, glial, neural, and immune cell populations in the tumor microenvironment. Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy. Here, we discuss the heterogeneity and relevant functions of tumor cell state, microglia, monocyte-derived macrophages, and neurons in glioma, highlighting their bilateral effects on tumors. Finally, we describe potential therapeutic approaches and targets beyond standard treatments.
Humans
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Glioma/metabolism*
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Neuroglia/metabolism*
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Carcinogenesis/pathology*
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Neural Stem Cells/metabolism*
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Microglia/metabolism*
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Brain Neoplasms/metabolism*
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Tumor Microenvironment