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Neural Stem Cell Grafts Promote Astroglia-Driven Neurorestoration in the Aged Parkinsonian Brain via Wnt/β-Catenin Signaling : Rejuvenation of the PD Brain by Grafted NSCs

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      A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function.

      Understanding the cell-cell interactions that control CNS development and function has long been limited by the lack of methods to cleanly separate neural cell types. Here we describe methods for the prospective isolation and purification of astrocytes, neurons, and oligodendrocytes from developing and mature mouse forebrain. We used FACS (fluorescent-activated cell sorting) to isolate astrocytes from transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of an S100beta promoter. Using Affymetrix GeneChip Arrays, we then created a transcriptome database of the expression levels of >20,000 genes by gene profiling these three main CNS neural cell types at various postnatal ages between postnatal day 1 (P1) and P30. This database provides a detailed global characterization and comparison of the genes expressed by acutely isolated astrocytes, neurons, and oligodendrocytes. We found that Aldh1L1 is a highly specific antigenic marker for astrocytes with a substantially broader pattern of astrocyte expression than the traditional astrocyte marker GFAP. Astrocytes were enriched in specific metabolic and lipid synthetic pathways, as well as the draper/Megf10 and Mertk/integrin alpha(v)beta5 phagocytic pathways suggesting that astrocytes are professional phagocytes. Our findings call into question the concept of a "glial" cell class as the gene profiles of astrocytes and oligodendrocytes are as dissimilar to each other as they are to neurons. This transcriptome database of acutely isolated purified astrocytes, neurons, and oligodendrocytes provides a resource to the neuroscience community by providing improved cell-type-specific markers and for better understanding of neural development, function, and disease.
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        Microglia: a sensor for pathological events in the CNS.

        The most characteristic feature of microglial cells is their rapid activation in response to even minor pathological changes in the CNS. Microglia activation is a key factor in the defence of the neural parenchyma against infectious diseases, inflammation, trauma, ischaemia, brain tumours and neurodegeneration. Microglia activation occurs as a graded response in vivo. The transformation of microglia into potentially cytotoxic cells is under strict control and occurs mainly in response to neuronal or terminal degeneration, or both. Activated microglia are mainly scavenger cells but also perform various other functions in tissue repair and neural regeneration. They form a network of immune alert resident macrophages with a capacity for immune surveillance and control. Activated microglia can destroy invading micro-organisms, remove potentially deleterious debris, promote tissue repair by secreting growth factors and thus facilitate the return to tissue homeostasis. An understanding of intercellular signalling pathways for microglia proliferation and activation could form a rational basis for targeted intervention on glial reactions to injuries in the CNS.
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          Neurotoxic reactive astrocytes are induced by activated microglia

          A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.
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            Author and article information

            Affiliations
            [1 ]Oasi Research Institute-IRCCS; Troina Italy
            [2 ]Dept of Clinical Neurosciences; Clifford Allbutt Building - Cambridge Biosciences Campus and NIHR Biomedical Research,Centre, University of Cambridge; Hills Road CB2 0HA Cambridge UK
            [3 ]Department of Biomedical and Biotechnological Sciences (BIOMETEC); Pharmacology and Physiology Sections, University of Catania Medical School; Catania Italy
            Journal
            STEM CELLS
            Stem Cells
            Wiley
            10665099
            August 2018
            August 2018
            April 16 2018
            : 36
            : 8
            : 1179-1197
            10.1002/stem.2827
            © 2018

            http://doi.wiley.com/10.1002/tdm_license_1.1

            http://onlinelibrary.wiley.com/termsAndConditions#vor

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