-
Neural Development Dec 2019Microglia are increasingly shown to be key players in neuron development and synapse connectivity. However, the underlying mechanisms by which microglia regulate neuron... (Review)
Review
Microglia are increasingly shown to be key players in neuron development and synapse connectivity. However, the underlying mechanisms by which microglia regulate neuron function remain poorly understood in part because such analysis is challenging in the brain where neurons and synapses are intermingled and connectivity is only beginning to be mapped. Here, we discuss the features and function of microglia in the ordered mammalian retina where the laminar organization of neurons and synapses facilitates such molecular studies. We discuss microglia origins and consider the evidence for molecularly distinct microglia subpopulations and their potential for differential roles with a particular focus on the early stages of retina development. We then review the models and methods used for the study of these cells and discuss emerging data that link retina microglia to the genesis and survival of particular retina cell subtypes. We also highlight potential roles for microglia in shaping the development and organization of the vasculature and discuss cellular and molecular mechanisms involved in this process. Such insights may help resolve the mechanisms by which retinal microglia impact visual function and help guide studies of related features in brain development and disease.
Topics: Animals; Microglia; Retina
PubMed: 31888774
DOI: 10.1186/s13064-019-0137-x -
Seminars in Cell & Developmental Biology Oct 2019Exposure to stressors disrupts homeostasis and results in the release of stress hormones including glucocorticoids, epinepherine and norepinepherine. Interestingly,... (Review)
Review
Exposure to stressors disrupts homeostasis and results in the release of stress hormones including glucocorticoids, epinepherine and norepinepherine. Interestingly, stress also has profound affects on microglia, which are tissue-resident macrophages in the brain parenchyma. Microglia express a diverse array of receptors, which also allows them to respond to stress hormones derived from peripheral as well as central sources. Here, we review studies of how exposure to acute and chronic stressors alters the immunophenotype and function of microglia. Further, we examine a causal for stress hormones in these effects of stress on microglia. We propose that microglia serve as immunosensors of the stress response, which puts them in the unique position to sense and respond rapidly to alterations in homeostasis and integrate the neural response to threats.
Topics: Animals; Humans; Microglia; Stress, Psychological
PubMed: 30638704
DOI: 10.1016/j.semcdb.2019.01.001 -
Cells Dec 2020Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune... (Review)
Review
Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune microenvironment. High dimensional data analysis reveals the extensive heterogeneity of immune components making up the GBM microenvironment. Myeloid cells are the most predominant contributors to the GBM microenvironment; these cells are critical regulators of immune and therapeutic responses to GBM. Here, we will review the most recent advances on the characteristics and functions of different populations of myeloid cells in GBM, including bone marrow-derived macrophages, microglia, myeloid-derived suppressor cells, dendritic cells, and neutrophils. Epigenetic, metabolic, and phenotypic peculiarities of microglia and bone marrow-derived macrophages will also be assessed. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in GBM patients.
Topics: Brain Neoplasms; Glioblastoma; Humans; Immunotherapy; Microglia; Myeloid Cells; Tumor Microenvironment
PubMed: 33374253
DOI: 10.3390/cells10010018 -
Frontiers in Immunology 2022The brain and spinal cord are immune-privileged organs, but in the disease state protection mechanisms such as the blood brain barrier (BBB) are ineffective or overcome... (Review)
Review
The brain and spinal cord are immune-privileged organs, but in the disease state protection mechanisms such as the blood brain barrier (BBB) are ineffective or overcome by pathological processes. In neuroinflammatory diseases, microglia cells and other resident immune cells contribute to local vascular inflammation and potentially a systemic inflammatory response taking place in parallel. Microglia cells interact with other cells impacting on the integrity of the BBB and propagate the inflammatory response through the release of inflammatory signals. Here, we discuss the activation and response mechanisms of innate and adaptive immune processes in response to neuroinflammation. Furthermore, the clinical importance of neuroinflammatory mediators and a potential translational relevance of involved mechanisms are addressed also with focus on non-classical immune cells including microglia cells or platelets. As illustrative examples, novel agents such as Anfibatide or Revacept, which result in reduced recruitment and activation of platelets, a subsequently blunted activation of the coagulation cascade and further inflammatory process, demonstrating that mechanisms of neuroinflammation and thrombosis are interconnected and should be further subject to in depth clinical and basic research.
Topics: Blood Platelets; Humans; Inflammation; Microglia; Thromboinflammation; Thrombosis
PubMed: 35309326
DOI: 10.3389/fimmu.2022.843404 -
Brain Research Bulletin Sep 2021Microglia are the major immune cells in the brain parenchyma. Besides their immune functions, microglia are important in regulating the dynamics of synapses. It is... (Review)
Review
Microglia are the major immune cells in the brain parenchyma. Besides their immune functions, microglia are important in regulating the dynamics of synapses. It is believed that the stability of synapses is essential for long-term storage and retrieval of memories, whereas microglial regulation of synaptic dynamics could affect the stability of memories, thus providing a potential mechanism for forgetting. In this review, we focus on the regulation of synaptic dynamics by microglia, as well as the subsequent effects on memory and forgetting, under physiological and pathological conditions. Revealing microglial regulation of synaptic dynamics will not only illuminate the physiological functions of microglia in the brain, but also provide us a new perspective to study the molecular and cellular mechanisms underlying forgetting. In addition, this will also improve our understanding of the process of memory encoding, storage and retrieval in the brain. Furthermore, uncovering the mechanisms through which microglia act on synaptic dynamics in pathological conditions will provide new strategies for the prevention and treatment of memory impairment in diseases.
Topics: Animals; Humans; Memory; Microglia; Neuronal Plasticity; Synapses
PubMed: 34129917
DOI: 10.1016/j.brainresbull.2021.06.005 -
Frontiers in Immunology 2021
Topics: Humans; Microglia; Retina
PubMed: 34539681
DOI: 10.3389/fimmu.2021.758375 -
Frontiers in Immunology 2022Recent epidemiological studies show a noticeable correlation between chronic microbial infections and neurological disorders. However, the underlying mechanisms are... (Review)
Review
Recent epidemiological studies show a noticeable correlation between chronic microbial infections and neurological disorders. However, the underlying mechanisms are still not clear due to the biological complexity of multicellular and multiorgan interactions upon microbial infections. In this review, we show the infection leading to neurodegeneration mediated by multiorgan interconnections and neuroinflammation. Firstly, we highlight three inter-organ communications as possible routes from infection sites to the brain: nose-brain axis, lung-brain axis, and gut-brain axis. Next, we described the biological crosstalk between microglia and astrocytes upon pathogenic infection. Finally, our study indicates how neuroinflammation is a critical player in pathogen-mediated neurodegeneration. Taken together, we envision that antibiotics targeting neuro-pathogens could be a potential therapeutic strategy for neurodegeneration.
Topics: Astrocytes; Brain; Humans; Microglia; Neuroinflammatory Diseases
PubMed: 36052093
DOI: 10.3389/fimmu.2022.907804 -
Journal of Neuroinflammation Mar 2021There are inherent structural and functional differences in the central nervous systems (CNS) of females and males. It has been gradually established that these... (Review)
Review
There are inherent structural and functional differences in the central nervous systems (CNS) of females and males. It has been gradually established that these sex-specific differences are due to a spectrum of genetic, epigenetic, and hormonal factors which actively contribute to the differential incidences, disease courses, and even outcomes of CNS diseases between sexes. Microglia, as principle resident macrophages in the CNS, play a crucial role in both CNS physiology and pathology. However, sex differences of microglia have been relatively unexplored until recently. Emerging data has convincingly demonstrated the existence of sex-dependent structural and functional differences of rodent microglia, consequently changing our current understanding of these versatile cells. In this review, we attempt to comprehensively outline the current advances revealing microglial sex differences in rodent and their potential implications for specific CNS diseases with a stark sex difference. A detailed understanding of molecular processes underlying microglial sex differences is of major importance in design of translational sex- and microglia-specific therapeutic approaches.
Topics: Animals; Epigenesis, Genetic; Female; Male; Microglia; Rodentia; Sex Characteristics
PubMed: 33731174
DOI: 10.1186/s12974-021-02124-z -
Cells Jul 2023The interaction between microglia and astrocytes exhibits a relatively balanced state in order to maintain homeostasis in the healthy central nervous system (CNS).... (Review)
Review
The interaction between microglia and astrocytes exhibits a relatively balanced state in order to maintain homeostasis in the healthy central nervous system (CNS). Disease stimuli alter microglia-astrocyte interaction patterns and elicit cell-type-specific responses, resulting in their contribution to various pathological processes. Here, we review the similarities and differences in the activation modes between microglia and astrocytes in various scenarios, encompassing different stages of neural development and a wide range of neural disorders. The aim is to provide a comprehensive understanding of their roles in neural development and regeneration and guiding new strategies for restoring CNS homeostasis.
Topics: Astrocytes; Microglia; Central Nervous System; Neurogenesis
PubMed: 37566021
DOI: 10.3390/cells12151942 -
Microglia reprogram metabolic profiles for phenotype and function changes in central nervous system.Neurobiology of Disease May 2021In response to various types of environmental and cellular stress, microglia rapidly activate and exhibit either pro- or anti-inflammatory phenotypes to maintain tissue... (Review)
Review
In response to various types of environmental and cellular stress, microglia rapidly activate and exhibit either pro- or anti-inflammatory phenotypes to maintain tissue homeostasis. Activation of microglia can result in changes in morphology, phagocytosis capacity, and secretion of cytokines. Furthermore, microglial activation also induces changes to cellular energy demand, which is dependent on the metabolism of various metabolic substrates including glucose, fatty acids, and amino acids. Accumulating evidence demonstrates metabolic reprogramming acts as a key driver of microglial immune response. For instance, microglia in pro-inflammatory states preferentially use glycolysis for energy production, whereas, cells in anti-inflammatory states are mainly powered by oxidative phosphorylation and fatty acid oxidation. In this review, we summarize recent findings regarding microglial metabolic pathways under physiological and pathological circumtances. We will then discuss how metabolic reprogramming can orchestrate microglial response to a variety of central nervous system pathologies. Finally, we highlight how manipulating metabolic pathways can reprogram microglia towards beneficial functions, and illustrate the therapeutic potential for inflammation-related neurological diseases.
Topics: Adaptation, Physiological; Animals; Cellular Reprogramming; Central Nervous System; Humans; Metabolome; Microglia; Phenotype
PubMed: 33556540
DOI: 10.1016/j.nbd.2021.105290