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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 -
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 -
Frontiers in Immunology 2022Traumatic optic neuropathy (TON) refers to a pathological condition caused by a direct or indirect insult to the optic nerves, which often leads to a partial or... (Review)
Review
Traumatic optic neuropathy (TON) refers to a pathological condition caused by a direct or indirect insult to the optic nerves, which often leads to a partial or permanent vision deficit due to the massive loss of retinal ganglion cells (RGCs) and their axonal fibers. Retinal microglia are immune-competent cells residing in the retina. In rodent models of optic nerve crush (ONC) injury, resident retinal microglia gradually become activated, form end-to-end alignments in the vicinity of degenerating RGC axons, and actively internalized them. Some activated microglia adopt an amoeboid morphology that engulf dying RGCs after ONC. In the injured optic nerve, the activated microglia contribute to the myelin debris clearance at the lesion site. However, phagocytic capacity of resident retinal microglia is extremely poor and therefore the clearance of cellular and myelin debris is largely ineffective. The presence of growth-inhibitory myelin debris and glial scar formed by reactive astrocytes inhibit the regeneration of RGC axons, which accounts for the poor visual function recovery in patients with TON. In this Review, we summarize the current understanding of resident retinal microglia in RGC survival and axon regeneration after ONC. Resident retinal microglia play a key role in facilitating Wallerian degeneration and the subsequent axon regeneration after ONC. However, they are also responsible for producing pro-inflammatory cytokines, chemokines, and reactive oxygen species that possess neurotoxic effects on RGCs. Intraocular inflammation triggers a massive influx of blood-borne myeloid cells which produce oncomodulin to promote RGC survival and axon regeneration. However, intraocular inflammation induces chronic neuroinflammation which exacerbates secondary tissue damages and limits visual function recovery after ONC. Activated retinal microglia is required for the proliferation of oligodendrocyte precursor cells (OPCs); however, sustained activation of retinal microglia suppress the differentiation of OPCs into mature oligodendrocytes for remyelination after injury. Collectively, controlled activation of retinal microglia and infiltrating myeloid cells facilitate axon regeneration and nerve repair. Recent advance in single-cell RNA-sequencing and identification of microglia-specific markers could improve our understanding on microglial biology and to facilitate the development of novel therapeutic strategies aiming to switch resident retinal microglia's phenotype to foster neuroprotection.
Topics: Axons; Humans; Microglia; Nerve Regeneration; Neuroinflammatory Diseases; Optic Nerve Injuries; Retinal Ganglion Cells
PubMed: 35309305
DOI: 10.3389/fimmu.2022.860070 -
Ageing Research Reviews Nov 2022Vascular dementia (VaD) is a second most common form of age-related dementia. It is characterized by cognitive impairment associated with vascular pathology, symptoms... (Review)
Review
Vascular dementia (VaD) is a second most common form of age-related dementia. It is characterized by cognitive impairment associated with vascular pathology, symptoms mainly caused by cerebral damage due to inadequate blood flow to the brain. The pathogenesis of VaD is complex, and a growing body of literature emphasizes on the involvement of microglia in disease development and progression. Here, we review the current knowledge on the role of microglia in regulating neuroinflammation under the pathogenesis of VaD. The commonly used animal and cell models for understanding the disease pathogenesis were summarized. The mechanisms by which microglia contribute to VaD are multifactorial, and we specifically focus on some of the predominant functions of microglia, including chemotaxis, secretory property, phagocytosis, and its crosstalk with other neurovascular unit cells. Finally, potential therapeutic strategies targeting microglia-modulated neuroinflammation are discussed.
Topics: Animals; Brain; Cognitive Dysfunction; Dementia, Vascular; Humans; Microglia
PubMed: 36113763
DOI: 10.1016/j.arr.2022.101734 -
Trends in Neurosciences Oct 2015Despite decades of intensive research, the biological mechanisms that causally underlie depression are still unclear, and therefore the development of novel effective... (Review)
Review
Despite decades of intensive research, the biological mechanisms that causally underlie depression are still unclear, and therefore the development of novel effective antidepressant treatments is hindered. Recent studies indicate that impairment of the normal structure and function of microglia, caused by either intense inflammatory activation (e.g., following infections, trauma, stroke, short-term stress, autoimmune or neurodegenerative diseases) or by decline and senescence of these cells (e.g., during aging, Alzheimer's disease, or chronic unpredictable stress exposure), can lead to depression and associated impairments in neuroplasticity and neurogenesis. Accordingly, some forms of depression can be considered as a microglial disease (microgliopathy), which should be treated by a personalized medical approach using microglial inhibitors or stimulators depending on the microglial status of the depressed patient.
Topics: Animals; Antidepressive Agents; Depressive Disorder; Electroconvulsive Therapy; Humans; Microglia; Precision Medicine
PubMed: 26442697
DOI: 10.1016/j.tins.2015.08.001 -
Glia Jul 2021Microglia are innate immune cells of the central nervous system that sense extracellular cues. Brain injuries, inflammation, and pathology evoke dynamic structural... (Review)
Review
Microglia are innate immune cells of the central nervous system that sense extracellular cues. Brain injuries, inflammation, and pathology evoke dynamic structural responses in microglia, altering their morphology and motility. The dynamic motility of microglia is hypothesized to be a critical first step in sensing local alterations and engaging in pattern-specific responses. Alongside their pathological responses, microglia also sense and regulate neuronal activity. In this review, we consider the extracellular molecules, receptors, and mechanisms that allow microglia to sense neuronal activity changes under both hypoactivity and hyperactivity. We also highlight emerging in vivo evidence that microglia regulate neuronal activity, ranging from physiological to pathophysiological conditions. In addition, we discuss the emerging role of calcium signaling in microglial responses to the extracellular environment. The dynamic function of microglia in monitoring and influencing neuronal activity may be critical for brain homeostasis and circuit modification in health and disease.
Topics: Brain; Calcium Signaling; Central Nervous System; Microglia; Neurons
PubMed: 33369790
DOI: 10.1002/glia.23961 -
Methods in Molecular Biology (Clifton,... 2019Microglia, the brain's resident macrophages, are incredibly plastic and dynamic cells. In this chapter, we aim to describe and classify the many morphological changes... (Review)
Review
Microglia, the brain's resident macrophages, are incredibly plastic and dynamic cells. In this chapter, we aim to describe and classify the many morphological changes they can display in normal development, aging, and disease. Although microglia in healthy adult brain tissue are often ramified with small somas, they can undergo massive and rapid morphological shifts in response to stimuli, becoming amoeboid or hypertrophic. Older animals occasionally contain dystrophic, senescent, and gitter cell-like microglia, and brain injury can be accompanied by an increase in rod cells. By a careful study of microglial morphology, coupled with ultrastructural insights gleaned using electron microscopy, insights can be provided into the functions performed by these various morphological phenotypes.
Topics: Animals; Brain; Brain Injuries; Humans; Microglia
PubMed: 31392674
DOI: 10.1007/978-1-4939-9658-2_2 -
Trends in Molecular Medicine Nov 2019Originally hypothesized to function solely as immunologic responders within the central nervous system (CNS), emerging evidence has revealed that microglia have more... (Review)
Review
Originally hypothesized to function solely as immunologic responders within the central nervous system (CNS), emerging evidence has revealed that microglia have more complex roles in normal brain development and in the context of disease. In health, microglia influence neural progenitor fate decisions, astrocyte activation, neuronal homeostasis, and synaptogenesis. In the setting of brain disease, including autism, brain tumors, and neurodegenerative disorders, microglia undergo substantial morphological, molecular, and functional changes, which establish new biological states relevant to disease pathogenesis and progression. In this review, we discuss the function of microglia in health and disease and outline a conceptual framework for elucidating their specific contributions to nervous system pathobiology.
Topics: Aging; Animals; Astrocytes; Autistic Disorder; Biomarkers; Brain; Brain Neoplasms; Cell Differentiation; Cellular Microenvironment; Central Nervous System; Homeostasis; Humans; Inflammation Mediators; Microglia; Neurodegenerative Diseases; Neurons; Synapses
PubMed: 31597593
DOI: 10.1016/j.molmed.2019.08.013 -
Journal of Visualized Experiments : JoVE Jun 2018Microglia are brain phagocytes that participate in brain homeostasis and continuously survey their environment for dysfunction, injury, and disease. As the first...
Microglia are brain phagocytes that participate in brain homeostasis and continuously survey their environment for dysfunction, injury, and disease. As the first responders, microglia have important functions to mitigate neuron and glia dysfunction, and in this process, they undergo a broad range of morphologic changes. Microglia morphologies can be categorized descriptively or, alternatively, can be quantified as a continuous variable for parameters such as cell ramification, complexity, and shape. While methods for quantifying microglia are applied to single cells, few techniques apply to multiple microglia in an entire photomicrograph. The purpose of this method is to quantify multiple and single cells using readily available ImageJ protocols. This protocol is a summary of the steps and ImageJ plugins recommended to convert fluorescence and bright-field photomicrographs into representative binary and skeletonized images and to analyze them using software plugins AnalyzeSkeleton (2D/3D) and FracLac for morphology data collection. The outputs of these plugins summarize cell morphology in terms of process endpoints, junctions, and length as well as complexity, cell shape, and size descriptors. The skeleton analysis protocol described herein is well suited for a regional analysis of multiple microglia within an entire photomicrograph or region of interest (ROI) whereas FracLac provides a complementary individual cell analysis. Combined, the protocol provides an objective, sensitive, and comprehensive assessment tool that can be used to stratify between diverse microglia morphologies present in the healthy and injured brain.
Topics: Animals; Immunohistochemistry; Mice; Microglia; Photomicrography; Rats
PubMed: 29939190
DOI: 10.3791/57648 -
Seminars in Cell & Developmental Biology Oct 2019The continuous crosstalk between microglia and neurons is required for microglia housekeeping functions and contributes to brain homeostasis. Through these exchanges,... (Review)
Review
The continuous crosstalk between microglia and neurons is required for microglia housekeeping functions and contributes to brain homeostasis. Through these exchanges, microglia take part in crucial brain functions, including development and plasticity. The alteration of neuron-microglia communication contributes to brain disease states with consequences, ranging from synaptic function to neuronal survival. This review focuses on the signaling pathways responsible for neuron-microglia crosstalk, highlighting their physiological roles and their alteration or specific involvement in disease. In particular, we discuss studies, establishing how these signaling allow microglial cells to control relevant physiological functions during brain development, including synaptic formation and circuit refinement. In addition, we highlight how microglia and neurons interact functionally to regulate highly dynamical synaptic functions. Microglia are able to release several signaling molecules involved in the regulation of synaptic activity and plasticity. On the other side, molecules of neuronal origin control microglial processes motility in an activity-dependent manner. Indeed, the continuous crosstalk between microglia and neurons is required for the sensing and housekeeping functions of microglia and contributes to the maintenance of brain homeostasis and, particularly, to the sculpting of neuronal connections during development. These interactions lay on the delicate edge between physiological processes and homeostasis alteration in pathology and are themselves altered during neuroinflammation. The full description of these processes could be fundamental for understanding brain functioning in health and disease.
Topics: Animals; Humans; Microglia; Neurons; Signal Transduction
PubMed: 31112798
DOI: 10.1016/j.semcdb.2019.05.017