Microglia/physiology* ; Neurons/physiology* ; Cells, Cultured

Glial cells, consisting of astrocytes, oligodendrocyte lineage cells, and microglia, account for >50% of the total number of cells in the mammalian brain. They play key roles in the modulation of various brain activities under physiological and pathological conditions. Although the typical morphological features and characteristic functions of these cells are well described, the organization of interconnections of the different glial cell populations and their impact on the healthy and diseased brain is not completely understood. Understanding these processes remains a profound challenge. Accumulating evidence suggests that glial cells can form highly complex interconnections with each other. The astroglial network has been well described. Oligodendrocytes and microglia may also contribute to the formation of glial networks under various circumstances. In this review, we discuss the structure and function of glial networks and their pathological relevance to central nervous system diseases. We also highlight opportunities for future research on the glial connectome.
Animals ; Neuroglia/physiology* ; Neurons/physiology* ; Astrocytes ; Microglia/physiology* ; Oligodendroglia ; Mammals

Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain. To better understand the microglial contribution to chronic pain, specific regional and temporal manipulations of microglia are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs (DREADDs) specifically in microglia. Similarly, optogenetic tools allow for microglial manipulation via the activation of artificially expressed, light-sensitive proteins. Chemo- and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain. This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.
Humans ; Optogenetics ; Brain/physiology* ; Microglia ; Chronic Pain/therapy* ; Neurons/physiology*

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 ; Central Nervous System ; cytology ; Humans ; Microglia ; immunology ; physiology

Encephalitis ; metabolism ; pathology ; Microglia ; metabolism ; pathology ; Receptors, Leukotriene ; metabolism ; physiology

Microglia are resident macrophages of central nervous system (CNS), and thus act as the crucial stuff of immune response and play very important roles in the progress of various CNS diseases. There are two different polarization statuses of activated microglia, M1 and M2 phenotypes. M1 polarized microglia are important for eradicating bacterial and promoting inflammation, whereas M2 cells are characterized by anti-inflammation and tissue remodeling. Recently, more and more evidence indicated that different polarized microglia showed diverse microRNA (miRNA) expression profiles. MiRNAs regulate microglia polarization, and thus affect the progress of CNS diseases. Fully exploring the polarization status of microglia during CNS diseases and the role of miRNAs in microglia polarization will be very helpful for a deep understanding of the roles of microglia in immunopathologic mechanism of different CNS diseases and offer the theoretical foundation of searching more effective therapies for these disorders.
Central Nervous System Diseases ; physiopathology ; Humans ; Inflammation ; Macrophages ; physiology ; MicroRNAs ; physiology ; Microglia ; physiology

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 ; Apoptosis ; Cell Line ; Humans ; Microglia/*cytology/*parasitology ; Naegleria fowleri/*physiology ; Phagocytosis/physiology

Microglial cells are widely distributed in the brain and spinal cord, and usually act as resident immune cells which could provide continuous monitoring roles within the central nervous system. When the cells in the central nervous system are injured, microglial cells are activated and induce a series of biological effects. Recently, several voltage-gated sodium channel subtypes were found to be expressed on the surface of the microglial cells which are able to participate in the regulation of the activation, phagocytosis, secretion of multiple cytokines/chemokines, migration, invasion of microglial cells, and etc. In the present study, the latest progresses on the regulation of voltage-gated sodium channel isoforms on microglial cells were summarized and analyzed. In addition, the mechanism and future research of the relationship between voltage-gated sodium channels and microglial cells were also discussed.
Animals ; Cytokines ; Humans ; Microglia ; physiology ; Protein Isoforms ; Voltage-Gated Sodium Channels ; physiology

As prominent immune cells in the central nervous system, microglia constantly monitor the environment and provide neuronal protection, which are important functions for maintaining brain homeostasis. In the diseased brain, microglia are crucial mediators of neuroinflammation that regulates a broad spectrum of cellular responses. In this review, we summarize current knowledge on the multifunctional contributions of microglia to homeostasis and their involvement in neurodegeneration. We further provide a comprehensive overview of therapeutic interventions targeting microglia in neurodegenerative diseases. Notably, we propose microglial depletion and subsequent repopulation as promising replacement therapy. Although microglial replacement therapy is still in its infancy, it will likely be a trend in the development of treatments for neurodegenerative diseases due to its versatility and selectivity.
Humans ; Microglia/physiology* ; Central Nervous System ; Neurodegenerative Diseases/therapy* ; Brain/physiology* ; Homeostasis

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 ; Cell Nucleus/metabolism* ; Forensic Medicine/methods* ; Microglia/physiology* ; NF-kappa B/physiology* ; Neurons/metabolism*