57
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Glial cells, consisting of microglia, astrocytes, and oligodendrocyte lineage cells as their major components, constitute a large fraction of the mammalian brain. Originally considered as purely non-functional glue for neurons, decades of research have highlighted the importance as well as further functions of glial cells. Although many aspects of these cells are well characterized nowadays, the functions of the different glial populations in the brain under both physiological and pathological conditions remain, at least to a certain extent, unresolved. To tackle these important questions, a broad range of depletion approaches have been developed in which microglia, astrocytes, or oligodendrocyte lineage cells (i.e., NG2-glia and oligodendrocytes) are specifically ablated from the adult brain network with a subsequent analysis of the consequences. As the different glial populations are very heterogeneous, it is imperative to specifically ablate single cell populations instead of inducing cell death in all glial cells in general. Thanks to modern genetic manipulation methods, the approaches can now directly be targeted to the cell type of interest making the ablation more specific compared to general cell ablation approaches that have been used earlier on. In this review, we will give a detailed summary on different glial ablation studies, focusing on the adult mouse central nervous system and the functional readouts. We will also provide an outlook on how these approaches could be further exploited in the future.

          Related collections

          Most cited references135

          • Record: found
          • Abstract: found
          • Article: not found

          Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo.

          Microglial cells represent the immune system of the mammalian brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. By using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood-brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patroling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in the adult brain.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Astrocytes: biology and pathology

            Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Development of monocytes, macrophages, and dendritic cells.

              Monocytes and macrophages are critical effectors and regulators of inflammation and the innate immune response, the immediate arm of the immune system. Dendritic cells initiate and regulate the highly pathogen-specific adaptive immune responses and are central to the development of immunologic memory and tolerance. Recent in vivo experimental approaches in the mouse have unveiled new aspects of the developmental and lineage relationships among these cell populations. Despite this, the origin and differentiation cues for many tissue macrophages, monocytes, and dendritic cell subsets in mice, and the corresponding cell populations in humans, remain to be elucidated.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Cell Neurosci
                Front Cell Neurosci
                Front. Cell. Neurosci.
                Frontiers in Cellular Neuroscience
                Frontiers Media S.A.
                1662-5102
                13 February 2017
                2017
                : 11
                : 24
                Affiliations
                [1] 1Physiological Genomics, Biomedical Center, Ludwig-Maximilians University Munich, Germany
                [2] 2MRC Centre for Regenerative Medicine, University of Edinburgh Edinburgh, UK
                [3] 3Munich Cluster for Systems Neurology Munich, Germany
                [4] 4Molecular and Translational Neuroscience, Department of Neurology, University of Ulm Ulm, Germany
                Author notes

                Edited by: Elena García-Martín, University of Extremadura, Spain

                Reviewed by: Ania K. Majewska, University of Rochester, USA; Marina Guizzetti, Oregon Health & Science University, USA

                *Correspondence: Sarah Jäkel, sarah.jaekel@ 123456ed.ac.uk
                Article
                10.3389/fncel.2017.00024
                5303749
                28243193
                d4d624bf-3e00-420c-ad56-e158a8f77a62
                Copyright © 2017 Jäkel and Dimou.

                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) or licensor 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.

                History
                : 07 October 2016
                : 26 January 2017
                Page count
                Figures: 4, Tables: 4, Equations: 0, References: 133, Pages: 17, Words: 0
                Categories
                Neuroscience
                Review

                Neurosciences
                cell ablation,astrocytes,microglia,ng2-glia,oligodendrocytes,brain function
                Neurosciences
                cell ablation, astrocytes, microglia, ng2-glia, oligodendrocytes, brain function

                Comments

                Comment on this article