1.Microglial Phagocytosis in the Neurodegenerative Diseases.
Sheng-nan CAO ; Xiu-qi BAO ; Hua SUN ; Dan ZHANG
Acta Academiae Medicinae Sinicae 2016;38(2):228-233
Microglia are the resident innate immune cells in the brain. Under endogenous or exogenous stimulates, they become activated and play an important role in the neurodegenerative diseases. Microglial phagocytosis is a process of receptor-mediated engulfment and degradation of apoptotic cells. In addition, microglia can phagocyte brain-specific cargo, such as myelin debris and abnormal protein aggregation. However, recent studies have shown that microglia can also phagocyte stressed-but-viable neurons, causing loss of neurons in the brain. Thus, whether microglial phagocytosis is beneficial or not in neurodegenerative disease remains controversial. This article reviews microglial phagocytosis related mechanisms and its potential roles in neurodegenerative diseases, with an attempt to provide new insights in the treatment of neurodegenerative diseases.
Humans
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Microglia
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cytology
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Neurodegenerative Diseases
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physiopathology
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Phagocytosis
2.Physiological properties and functions of microglia.
Ying LI ; Xu-Fei DU ; Jiu-Lin DU
Acta Physiologica Sinica 2013;65(5):471-482
Microglia, the resident immune effective cells of the central nervous system, play crucial roles in mediating immune-related process. It becomes activated quickly in response to even minor pathological insults and participates in series of immune responses. Under physiological conditions, most microglia stay in a typical resting state, with ramified processes continuously extending and retracting from surrounding neural tissues, suggesting an important function of resting microglia. Recent studies indicate that resting microglia can regulate many physiological processes, including neural development, neural circuit formation, neuronal activity and plasticity, and animal grooming behavior. Here, we review the properties of resting microglia and further discuss how microglia participate in the above-mentioned functional regulation under physiological conditions.
Animals
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Central Nervous System
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cytology
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Humans
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Microglia
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immunology
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physiology
4.Contact-Independent Cell Death of Human Microglial Cells due to Pathogenic Naegleria fowleri Trophozoites.
Jong Hyun KIM ; Daesik KIM ; Ho Joon SHIN
The Korean Journal of Parasitology 2008;46(4):217-221
Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increasse of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.
Animals
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Apoptosis
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Cell Line
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Humans
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Microglia/*cytology/*parasitology
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Naegleria fowleri/*physiology
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Phagocytosis/physiology
6.Comprehensive therapeutics targeting the corticospinal tract following spinal cord injury.
An-Kai XU ; Zhe GONG ; Yu-Zhe HE ; Kai-Shun XIA ; Hui-Min TAO
Journal of Zhejiang University. Science. B 2019;20(3):205-218
Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.
Animals
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Astrocytes/cytology*
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Axons/physiology*
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Cell Transplantation
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Disease Models, Animal
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Electric Stimulation
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Humans
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Microglia/cytology*
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Motor Neurons/cytology*
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Nerve Regeneration
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Neuroglia/cytology*
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Neuronal Plasticity
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Neurons/cytology*
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Oligodendroglia/cytology*
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Pyramidal Tracts/pathology*
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Recovery of Function
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Regenerative Medicine/methods*
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Spinal Cord Injuries/therapy*
7.Naegleria fowleri Lysate Induces Strong Cytopathic Effects and Pro-inflammatory Cytokine Release in Rat Microglial Cells.
Yang Jin LEE ; Chang Eun PARK ; Jong Hyun KIM ; Hae Jin SOHN ; Jinyoung LEE ; Suk Yul JUNG ; Ho Joon SHIN
The Korean Journal of Parasitology 2011;49(3):285-290
Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A 51Cr release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-alpha, IL-6, and IL-1beta, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.
Animals
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*Cell Death
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Chromium Radioisotopes/metabolism
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Cytokines/*secretion
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Humans
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Microglia/cytology/immunology/*physiology
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Microscopy
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Naegleria fowleri/*pathogenicity
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Rats
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Staining and Labeling
8.A modified protocol of mouse hippocampal primary microglia culture by using manual dissociation, magnetic activated cell sorting and TIC medium.
Ya-Nan XU ; Li-Jun ZHOU ; Ying-Tao JIE ; Chun-Lin MAI ; Jun ZHANG ; Zhen-Jia LIN ; Zhi TAN
Acta Physiologica Sinica 2019;71(6):883-893
In this study, we improved the culture method of mouse hippocampal primary microglia to obtain hippocampal ramified microglia with high activity and purity, which were resemble to the resting status of normal microglia in healthy brain in vivo. Hippocampal tissue was excised from 2-4-week-old SPF C57BL/6J mice and cut into pieces after PBS perfusion, and then manually dissociated into the single-cell suspension by using Miltenyi Biotec's Adult Brain Dissociation Kit. The tissue fragments such as myelin in the supernatant were removed by debris removal solution in the kit. The cell suspension was incubated with CD11b immunomagnetic beads for 15 min at 4 °C. To obtain high-purity microglia, we used two consecutive cell-sorting steps by magnetic activated cell sorting (MACS). After centrifugation, the cells were resuspended and seeded in a 24-well culture plate. The primary microglia were cultured with complete medium (CM) or TIC medium (a serum-free medium with TGF-β, IL-34 and cholesterol as the main nutritional components) for 4 days, and then were used for further experiments. The results showed that: (1) The cell viability was (56.03 ± 2.10)% by manual dissociation of hippocampus; (2) Compared with immunopanning, two-step MACS sorting allowed for efficient enrichment of microglia with higher purity of (86.20 ± 0.68)%; (3) After being incubated in TIC medium for 4 d, microglia exhibited branching, quiescent morphology; (4) The results from qRT-PCR assay showed that the levels of TNF-α, IL-1β and CCL2 mRNA in TIC cultured-microglia were similar to freshly isolated microglia, while those were much higher in CM cultured-microglia after incubation for 4 d and 7 d (P < 0.05). Taken together, compared to the conventional approaches, this modified protocol of mouse hippocampal primary microglia culture by using MACS and TIC medium enables the increased yield and purity of microglia in the quiescent state, which is similar to normal ramified microglia in healthy brain in vivo.
Animals
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Cell Culture Techniques
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methods
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Cell Separation
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methods
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Cells, Cultured
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Hippocampus
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Magnetics
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Mice
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Mice, Inbred C57BL
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Microglia
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cytology
9.Characteristic of microglial activation of hippocampus in experimental epileptic rats.
Hong SUN ; Hai-qin WU ; Gui-lian ZHANG ; Shu-qin ZHAN ; Ru ZHANG ; Hu-qing WANG
Journal of Zhejiang University. Medical sciences 2012;41(3):310-314
OBJECTIVETo investigate the characteristics of microglial activation of hippocampus in experimental epileptic rats.
METHODSMorphological changes and proliferation of OX-42 positive cells were compared at different time points after status of epilepticus (SE) in lithium-pilocarpine induced epileptic rats.
RESULTSOX-42 positive cells were activated after SE, which increased to a peak at 3-7 d and in a relatively stable state at 7-14 d; then gradually decreased after 14d and returned to slightly higher level than previously at 21 d.
CONCLUSIONInflammatory injury, microglial activation and cell proliferation are closely related after seizures, microglial activation may be an important mechanism in the inflammatory injury of epilepsy.
Animals ; Cell Proliferation ; Disease Models, Animal ; Hippocampus ; cytology ; pathology ; Male ; Microglia ; pathology ; Rats ; Rats, Sprague-Dawley ; Status Epilepticus ; pathology
10.Intrathecal Lamotrigine Attenuates Antinociceptive Morphine Tolerance and Suppresses Spinal Glial Cell Activation in Morphine-Tolerant Rats.
In Gu JUN ; Sung Hoon KIM ; Yang In YOON ; Jong Yeon PARK
Journal of Korean Medical Science 2013;28(2):300-307
Glial cells play a critical role in morphine tolerance, resulting from repeated administration of morphine. Both the development and the expression of tolerance are suppressed by the analgesic lamotrigine. This study investigated the relationship between the ability of lamotrigine to maintain the antinociceptive effect of morphine during tolerance development and glial cell activation in the spinal cord. In a rat model, morphine (15 microg) was intrathecally injected once daily for 7 days to induce morphine tolerance. Lamotrigine (200 microg) was co-administered with morphine either for 7 days or the first or last 3 days of this 7 day period. Thermal nociception was measured. OX-42 and GFAP immunoreactivity, indicating spinal microglial and astrocytic activation were evaluated on day 8. Tolerance developed after 7 days of intrathecal morphine administration; however, this was completely blocked and reversed by co-administration of lamotrigine. When lamotrigine was coinjected with morphine on days 5-7, the morphine effect was partially restored. Glial cell activation increased with the development of morphine tolerance but was clearly inhibited in the presence of lamotrigine. These results suggest that, in association with the suppression of spinal glial cell activity, intrathecally coadministered lamotrigine attenuates antinociceptive tolerance to morphine.
Analgesics/*pharmacology
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Animals
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Antigens, CD11b/metabolism
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Astrocytes/cytology
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Drug Tolerance
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Immunohistochemistry
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Male
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Microglia/cytology
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Morphine/*pharmacology
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Nerve Tissue Proteins/metabolism
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Neuroglia/cytology/*metabolism
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Rats
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Rats, Sprague-Dawley
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Spinal Cord/*cytology
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Triazines/*pharmacology