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Translational Neurodegeneration Nov 2020Neuroinflammation is associated with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Microglia and... (Review)
Review
Neuroinflammation is associated with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system. The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxic (M1-phenotype microglia and A1-phenotype astrocytes) or neuroprotective (M2-phenotype microglia and A2-phenotype astrocytes). However, this dichotomized classification may not reflect the various phenotypes of microglia and astrocytes. The relationship between these activated glial cells is also very complicated, and the phenotypic distribution can change, based on the progression of neurodegenerative diseases. A better understanding of the roles of microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies. In this review, we discuss the roles of inflammatory response in neurodegenerative diseases, focusing on the contributions of microglia and astrocytes and their relationship. In addition, we discuss biomarkers to measure neuroinflammation and studies on therapeutic drugs that can modulate neuroinflammation.
Topics: Animals; Astrocytes; Humans; Inflammation; Inflammation Mediators; Microglia; Neurodegenerative Diseases
PubMed: 33239064
DOI: 10.1186/s40035-020-00221-2 -
Immunity Oct 2021As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during... (Review)
Review
As resident macrophages of the central nervous system (CNS), microglia are associated with diverse functions essential to the developing and adult brain during homeostasis and disease. They are aided in their tasks by intricate bidirectional communication with other brain cells under steady-state conditions as well as with infiltrating peripheral immune cells during perturbations. Harmonious cell-cell communication involving microglia are considered crucial to maintain the healthy state of the tissue environment and to overcome pathology such as neuroinflammation. Analyses of such intercellular pathways have contributed to our understanding of the heterogeneous but context-associated microglial responses to environmental cues across neuropathology, including inflammatory conditions such as infections and autoimmunity, as well as immunosuppressive states as seen in brain tumors. Here, we summarize the latest evidence demonstrating how these interactions drive microglia immune and non-immune functions, which coordinate the transition from homeostatic to disease-related cellular states.
Topics: Animals; Central Nervous System; Homeostasis; Humans; Microglia
PubMed: 34644556
DOI: 10.1016/j.immuni.2021.09.014 -
Cell Oct 2019Microglia were first recognized as a distinct cell population in the CNS one century ago. For a long time, they were primarily considered to be phagocytes responsible... (Review)
Review
Microglia were first recognized as a distinct cell population in the CNS one century ago. For a long time, they were primarily considered to be phagocytes responsible for removing debris during CNS development and disease. More recently, advances in imaging and genetics and the advent of single-cell technologies provided new insights into the much more complex and fascinating biology of microglia. The ontogeny of microglia was identified, and their functions in health and disease were better defined. Although many questions about microglia and their roles in human diseases remain unanswered, the prospect of targeting microglia for the treatment of neurological and psychiatric disorders is tantalizing.
Topics: Animals; Homeostasis; Humans; Microglia; Neurodegenerative Diseases; Neurogenesis; Transcriptome
PubMed: 31585077
DOI: 10.1016/j.cell.2019.08.053 -
Science China. Life Sciences Jun 2021Major depressive disorder (MDD) is a prevalent psychiatric disease that involves malfunctions of different cell types in the brain. Accumulating studies started to... (Review)
Review
Major depressive disorder (MDD) is a prevalent psychiatric disease that involves malfunctions of different cell types in the brain. Accumulating studies started to reveal that microglia, the primary resident immune cells, play an important role in the development and progression of depression. Microglia respond to stress-triggered neuroinflammation, and through the release of proinflammatory cytokines and their metabolic products, microglia may modulate the function of neurons and astrocytes to regulate depression. In this review, we focused on the role of microglia in the etiology of depression. We discussed the dynamic states of microglia; the correlative and causal evidence of microglial abnormalities in depression; possible mechanisms of how microglia sense depression-related stress and modulate depression state; and how antidepressive therapies affect microglia. Understanding the role of microglia in depression may shed light on developing new treatment strategies to fight against this devastating mental illness.
Topics: Animals; Antidepressive Agents; Depressive Disorder, Major; Humans; Microglia
PubMed: 33068286
DOI: 10.1007/s11427-020-1815-6 -
Cell Reports Feb 2020Microglia are resident immune cells in the central nervous system (CNS) that are capable of carrying out prominent and various functions during development and adulthood... (Review)
Review
Microglia are resident immune cells in the central nervous system (CNS) that are capable of carrying out prominent and various functions during development and adulthood under both homeostatic and disease conditions. Although microglia are traditionally thought to be heterogeneous populations, which potentially allows them to achieve a wide range of responses to environmental changes for the maintenance of CNS homeostasis, a lack of unbiased and high-throughput methods to assess microglia heterogeneity has prevented the study of spatially and temporally distributed microglia subsets. The recent emergence of novel single-cell techniques, such as cytometry by time-of-flight mass spectrometry (CyTOF) and single-cell RNA sequencing, enabled scientists to overcome such limitations and reveal the surprising context-dependent heterogeneity of microglia. In this review, we summarize the current knowledge about the spatial, temporal, and functional diversity of microglia during development, homeostasis, and disease in mice and humans.
Topics: Aging; Animals; Brain; Homeostasis; Humans; Macrophages; Microglia; Single-Cell Analysis
PubMed: 32023447
DOI: 10.1016/j.celrep.2020.01.010 -
Nature Reviews. Neurology Apr 2023Interactions between the immune and nervous systems are of central importance in neuropathic pain, a common and debilitating form of chronic pain caused by a lesion or... (Review)
Review
Interactions between the immune and nervous systems are of central importance in neuropathic pain, a common and debilitating form of chronic pain caused by a lesion or disease affecting the somatosensory system. Our understanding of neuroimmune interactions in pain research has advanced considerably. Initially considered as passive bystanders, then as culprits in the pathogenesis of neuropathic pain, immune responses in the nervous system are now established to underpin not only the initiation and progression of pain but also its resolution. Indeed, immune cells and their mediators are well-established promoters of neuroinflammation at each level of the neural pain pathway that contributes to pain hypersensitivity. However, emerging evidence indicates that specific subtypes of immune cells (including antinociceptive macrophages, pain-resolving microglia and T regulatory cells) as well as immunoresolvent molecules and modulators of the gut microbiota-immune system axis can reduce the pain experience and contribute to the resolution of neuropathic pain. This Review provides an overview of the immune mechanisms responsible for the resolution of neuropathic pain, including those involved in innate, adaptive and meningeal immunity as well as interactions with the gut microbiome. Specialized pro-resolving mediators and therapeutic approaches that target these neuroimmune mechanisms are also discussed.
Topics: Humans; Neuralgia; Microglia; Chronic Pain; Immune System
PubMed: 36859719
DOI: 10.1038/s41582-023-00777-3 -
Developmental Neurobiology Jan 2022Microglia are important immune cells in the central nervous system. There is growing interest in the study of microglia due to their implication in neurodevelopment,... (Review)
Review
Microglia are important immune cells in the central nervous system. There is growing interest in the study of microglia due to their implication in neurodevelopment, acute injury, and neuropsychiatric disorders. They undergo birth, death, and regeneration during the lifetime. Although data on the ontogeny of microglia have been studied for decades, the birth and repopulation of microglia remain legendary and mysterious. In this review, we discuss recent studies that provide new insights into the origin and regeneration of microglia. Modulating the development of microglia may offer new therapeutic opportunities for preventing deleterious effects of inflammation and controlling excessive inflammation in brain diseases.
Topics: Brain; Central Nervous System; Humans; Inflammation; Microglia
PubMed: 34874111
DOI: 10.1002/dneu.22862 -
Glia Apr 2020The human retina contains three types of glial cells: microglia and two types of macroglia, astrocytes and Müller cells. Macroglia provide homeostatic and metabolic... (Review)
Review
The human retina contains three types of glial cells: microglia and two types of macroglia, astrocytes and Müller cells. Macroglia provide homeostatic and metabolic support to photoreceptors and neurons required for neuronal activity. The fovea, the site of the sharpest vision which is astrocyte- and microglia-free, contains two populations of Müller glia: cells which form the Müller cell cone in the foveola and z-shaped Müller cells of the foveal walls. Both populations are characterized by morphological and functional differences. Müller cells of the foveola do not support the activity of photoreceptors and neurons, but provide the structural stability of the foveal tissue and improve the light transmission through the tissue to the photoreceptors. This article gives overviews of the glia of the human retina and the structure and function of both Müller cell types in the fovea, and describes the contributions of astrocytes and Müller cells to the ontogenetic development of the fovea.
Topics: Astrocytes; Ependymoglial Cells; Humans; Microglia; Retina
PubMed: 31793693
DOI: 10.1002/glia.23727 -
Immunity Feb 2020Recent years have witnessed a revolution in our understanding of microglia biology, including their major role in the etiology and pathogenesis of neurodegenerative... (Review)
Review
Recent years have witnessed a revolution in our understanding of microglia biology, including their major role in the etiology and pathogenesis of neurodegenerative diseases. Technological advances have enabled the identification of microglial signatures in health and disease, including the development of new models to investigate and manipulate human microglia in vivo in the context of disease. In parallel, genetic association studies have identified several gene risk factors associated with Alzheimer's disease that are specifically or highly expressed by microglia in the central nervous system (CNS). Here, we discuss evidence for the effect of stress, diet, sleep patterns, physical activity, and microbiota composition on microglia biology and consider how lifestyle might influence an individual's predisposition to neurodegenerative diseases. We discuss how different lifestyles and environmental factors might regulate microglia, potentially leading to increased susceptibility to neurodegenerative disease, and we highlight the need to investigate the contribution of modern environmental factors on microglia modulation in neurodegeneration.
Topics: Aging; Animals; Central Nervous System; Circadian Rhythm; Exercise; Feeding Behavior; Genetic Predisposition to Disease; Humans; Life Style; Microbiota; Microglia; Neurodegenerative Diseases; Sleep; Stress, Psychological
PubMed: 31924476
DOI: 10.1016/j.immuni.2019.12.003 -
Seminars in Cell & Developmental Biology Oct 2019Microglia, being the resident immune cells of the central nervous system, play an important role in maintaining tissue homeostasis and contributes towards brain... (Review)
Review
Microglia, being the resident immune cells of the central nervous system, play an important role in maintaining tissue homeostasis and contributes towards brain development under normal conditions. However, when there is a neuronal injury or other insult, depending on the type and magnitude of stimuli, microglia will be activated to secrete either proinflammatory factors that enhance cytotoxicity or anti-inflammatory neuroprotective factors that assist in wound healing and tissue repair. Excessive microglial activation damages the surrounding healthy neural tissue, and the factors secreted by the dead or dying neurons in turn exacerbate the chronic activation of microglia, causing progressive loss of neurons. It is the case observed in many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. This review gives a detailed account of the microglia-mediated neuroinflammation in various neurodegenerative diseases. Hence, resolving chronic inflammation mediated by microglia bears great promise as a novel treatment strategy to reduce neuronal damage and to foster a permissive environment for further regeneration effort.
Topics: Animals; Humans; Inflammation; Microglia; Neurodegenerative Diseases
PubMed: 31077796
DOI: 10.1016/j.semcdb.2019.05.004