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      Neuroprotective function of microglia in the developing brain

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      Author(s): ,
      Publication date (Electronic):
      Journal: Neuronal Signaling
      Publisher: Portland Press Ltd.
      Keywords: brain, cell death, microglia, neuron, neurotrophic factors

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          Abstract

          Microglia are the resident immune cells of the central nervous system and are important for immune processes. Besides their classical roles in pathological conditions, these cells also dynamically interact with neurons and influence their structure and function in physiological conditions. Recent evidence revealed their role in healthy brain homeostasis, including the regulation of neurogenesis, cell survival, and synapse maturation and elimination, especially in the developing brain. In this review, we summarize the current state of knowledge on microglia in brain development, with a focus on their neuroprotective function. We will also discuss how microglial dysfunction may lead to the impairment of brain function, thereby contributing to disease development.

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          Fate mapping analysis reveals that adult microglia derive from primitive macrophages.

          Florent Ginhoux, Melanie Greter, Marylène Leboeuf … (2010)
          Microglia are the resident macrophages of the central nervous system and are associated with the pathogenesis of many neurodegenerative and brain inflammatory diseases; however, the origin of adult microglia remains controversial. We show that postnatal hematopoietic progenitors do not significantly contribute to microglia homeostasis in the adult brain. In contrast to many macrophage populations, we show that microglia develop in mice that lack colony stimulating factor-1 (CSF-1) but are absent in CSF-1 receptor-deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors that arise before embryonic day 8. These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.
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            Synaptic pruning by microglia is necessary for normal brain development.

            Rosa Paolicelli, Giulia Bolasco, Francesca Pagani … (2011)
            Microglia are highly motile phagocytic cells that infiltrate and take up residence in the developing brain, where they are thought to provide a surveillance and scavenging function. However, although microglia have been shown to engulf and clear damaged cellular debris after brain insult, it remains less clear what role microglia play in the uninjured brain. Here, we show that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice. These findings link microglia surveillance to synaptic maturation and suggest that deficits in microglia function may contribute to synaptic abnormalities seen in some neurodevelopmental disorders.
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              Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner.

              Dorothy P Schafer, Emily Lehrman, Amanda Kautzman … (2012)
              Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and that engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses. Copyright © 2012 Elsevier Inc. All rights reserved.
              Article 0 comments Cited 860 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yuki Fujita
                Toshihide Yamashita
                Journal
                Journal ID (publisher-id): ns
                Title: Neuronal Signaling
                Abbreviated Title: Neuronal Signal.
                Abbreviated Title: NS
                Publisher: Portland Press Ltd.
                ISSN (Electronic): 2059-6553
                Publication date Cover: April 2021
                Publication date Collection: 23 April 2021
                Publication date (Electronic): 22 January 2021
                Volume: 5
                Issue: 1
                Electronic Location Identifier: NS20200024
                Affiliations
                [1 ]Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
                [2 ]WPI Immunology Frontier Research Center, Osaka University, 3-1, Yamadaoka, Suita, Osaka 565-0871, Japan
                [3 ]Graduate School of Frontier Bioscience, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
                [4 ]Department of Neuro-Medical Science, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
                Author notes
                Correspondence: Yuki Fujita ( yuki-fujita@ 123456molneu.med.osaka-u.ac.jp ) or Toshihide Yamashita ( yamashita@ 123456molneu.med.osaka-u.ac.jp )
                Article
                Publisher ID: NS20200024
                DOI: 10.1042/NS20200024
                PMC ID: 7823182
                PubMed ID: 33532089
                SO-VID: 446e0b44-b7f6-484e-8f78-26aa01b95c91
                Copyright © © 2021 The Author(s).
                License:

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                Date received : 15 October 2020
                Date revision received : 03 January 2021
                Date accepted : 05 January 2021
                Date: 06 January 2021
                Page count
                Pages: 10
                Categories
                Subject: Neuroscience
                Subject: Immunology & Inflammation
                Subject: Cell Death & Injury
                Subject: Cell Migration, Adhesion & Morphology
                Subject: Review Articles

                ScienceOpen disciplines: Neurology,Molecular medicine,Molecular biology,Neurosciences
                Keywords: neurotrophic factors,cell death,brain,neuron,microglia
                Data availability:
                ScienceOpen disciplines: Neurology, Molecular medicine, Molecular biology, Neurosciences
                Keywords: neurotrophic factors, cell death, brain, neuron, microglia

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