Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7-mediated chondroitin sulfate proteoglycan production.

Autor: Kamermans A; Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, MS center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Planting KE; Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, MS center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Jalink K; Department of Cell Biology, The Netherlands Cancer Institute, Amsterdam, the Netherlands., van Horssen J; Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, MS center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., de Vries HE; Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, MS center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Glia [Glia] 2019 Jan; Vol. 67 (1), pp. 68-77. Date of Electronic Publication: 2018 Nov 19.
DOI: 10.1002/glia.23526
Abstrakt: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), characterized by inflammation-mediated demyelination, axonal injury and neurodegeneration. The mechanisms underlying impaired neuronal function are not fully understood, but evidence is accumulating that the presence of the gliotic scar produced by reactive astrocytes play a critical role in these detrimental processes. Here, we identified astrocytic Transient Receptor Potential cation channel, subfamily M, member 7 (TRPM7), a Ca 2+ -permeable nonselective cation channel, as a novel player in the formation of a gliotic scar. TRPM7 was found to be highly expressed in reactive astrocytes within well-characterized MS lesions and upregulated in primary astrocytes under chronic inflammatory conditions. TRPM7 overexpressing astrocytes impaired neuronal outgrowth in vitro by increasing the production of chondroitin sulfate proteoglycans, a key component of the gliotic scar. These findings indicate that astrocytic TRPM7 is a critical regulator of the formation of a gliotic scar and provide a novel mechanism by which reactive astrocytes affect neuronal outgrowth.
(© 2018 The Authors. Glia published by Wiley Periodicals, Inc.)
Databáze: MEDLINE
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