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      Crosstalk Between Astrocytes and Microglia: An Overview


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          Based on discoveries enabled by new technologies and analysis using novel computational tools, neuroscience can be re-conceived in terms of information exchange in dense networks of intercellular connections rather than in the context of individual populations, such as glia or neurons. Cross-talk between neurons and microglia or astrocytes has been addressed, however, the manner in which non-neuronal cells communicate and interact remains less well-understood. We review this intriguing crosstalk among CNS cells, focusing on astrocytes and microglia and how it contributes to brain development and neurodegenerative diseases. The goal of studying these intercellular communications is to promote our ability to combat incurable neurological disorders.

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          Microglia and macrophages in brain homeostasis and disease

          Microglia and non-parenchymal macrophages in the brain are mononuclear phagocytes that are increasingly recognized to be essential players in the development, homeostasis and diseases of the central nervous system. With the availability of new genetic, molecular and pharmacological tools, considerable advances have been made towards our understanding of the embryonic origins, developmental programmes and functions of these cells. These exciting discoveries, some of which are still controversial, also raise many new questions, which makes brain macrophage biology a fast-growing field at the intersection of neuroscience and immunology. Here, we review the current knowledge of how and where brain macrophages are generated, with a focus on parenchymal microglia. We also discuss their normal functions during development and homeostasis, the disturbance of which may lead to various neurodegenerative and neuropsychiatric diseases.
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            Diversity of astrocyte functions and phenotypes in neural circuits.

            Astrocytes tile the entire CNS. They are vital for neural circuit function, but have traditionally been viewed as simple, homogenous cells that serve the same essential supportive roles everywhere. Here, we summarize breakthroughs that instead indicate that astrocytes represent a population of complex and functionally diverse cells. Physiological diversity of astrocytes is apparent between different brain circuits and microcircuits, and individual astrocytes display diverse signaling in subcellular compartments. With respect to injury and disease, astrocytes undergo diverse phenotypic changes that may be protective or causative with regard to pathology in a context-dependent manner. These new insights herald the concept that astrocytes represent a diverse population of genetically tractable cells that mediate neural circuit-specific roles in health and disease.
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              Cell Biology of Astrocyte-Synapse Interactions

              Astrocytes, the most abundant glial cells in the mammalian brain, are critical regulators of brain development and physiology through dynamic and often bidirectional interactions with neuronal synapses. Despite the clear importance of astrocytes for the establishment and maintenance of proper synaptic connectivity, our understanding of their role in brain function is still in its infancy. We propose that this is at least in part due to large gaps in our knowledge of the cell biology of astrocytes and the mechanisms they use to interact with synapses. In this review, we summarize some of the seminal findings that yield important insight into the cellular and molecular basis of astrocyte-neuron communication, focusing on the role of astrocytes in the development and remodeling of synapses. Furthermore, we will pose some pressing questions that need to be addressed to advance our mechanistic understanding of the role of astrocytes in regulating synaptic development.

                Author and article information

                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                16 July 2020
                : 11
                : 1416
                [1] 1Department of Immunology, Collegium Medicum, University of Zielona Góra , Zielona Góra, Poland
                [2] 2Third Rock Ventures , Boston, MA, United States
                [3] 3Department of Cell Biology, Harvard Medical School , Boston, MA, United States
                Author notes

                Edited by: Tuan Leng Tay, University of Freiburg, Germany

                Reviewed by: Anna Molofsky, University of California, San Francisco, United States; Richa Hanamsagar, Massachusetts General Hospital, United States

                *Correspondence: Richard M. Ransohoff rransohoff@ 123456thirdrockventures.com

                This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Immunology

                Copyright © 2020 Matejuk and Ransohoff.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 28 October 2019
                : 02 June 2020
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 90, Pages: 11, Words: 9409

                microglia,astrocytes,neurons,glia,cns,neurological disorders,neurodegeneration
                microglia, astrocytes, neurons, glia, cns, neurological disorders, neurodegeneration


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