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CSF1R blockade slows the progression of amyotrophic lateral sclerosis by reducing microgliosis and invasion of macrophages into peripheral nerves
Martínez Muriana, Anna (Universitat Autònoma de Barcelona. Institut de Neurociències)
Mancuso, Renzo (Universitat Autònoma de Barcelona. Institut de Neurociències)
Francos Quijorna, Isaac (Universitat Autònoma de Barcelona. Institut de Neurociències)
Olmos Alonso, Adrian (University of Southampton. Centre for Biological Sciences)
Osta, Rosario (Universidad de Zaragoza)
Perry, V. Hugh (University of Southampton. Centre for Biological Sciences)
Navarro, X. (Xavier) (Xavier) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Gomez-Nicola, Diego (University of Southampton. Centre for Biological Sciences)
López Vales, Rubén (Universitat Autònoma de Barcelona. Institut de Neurociències)

Date: 2016
Abstract: Inflammation is a common neuropathological feature in several neurological disorders, including amyotrophic lateral sclerosis (ALS). We have studied the contribution of CSF1R signalling to inflammation in ALS, as a pathway previously reported to control the expansion and activation of microglial cells. We found that microglial cell proliferation in the spinal cord of SOD1(G93A) transgenic mice correlates with the expression of CSF1R and its ligand CSF1. Administration of GW2580, a selective CSF1R inhibitor, reduced microglial cell proliferation in SOD1(G93A) mice, indicating the importance of CSF1-CSF1R signalling in microgliosis in ALS. Moreover, GW2580 treatment slowed disease progression, attenuated motoneuron cell death and extended survival of SOD1(G93A) mice. Electrophysiological assessment revealed that GW2580 treatment protected skeletal muscle from denervation prior to its effects on microglial cells. We found that macrophages invaded the peripheral nerve of ALS mice before CSF1R-induced microgliosis occurred. Interestingly, treatment with GW2580 attenuated the influx of macrophages into the nerve, which was partly caused by the monocytopenia induced by CSF1R inhibition. Overall, our findings provide evidence that CSF1R signalling regulates inflammation in the central and peripheral nervous system in ALS, supporting therapeutic targeting of CSF1R in this disease.
Grants: European Commission 249274
Ministerio de Economía y Competitividad SAF2013-48431-R
Note: Altres ajuts: MR/K022687/1
Rights: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Language: Anglès
Document: Article ; recerca ; Versió publicada
Subject: Amyotrophic lateral sclerosis ; Neuroimmunology
Published in: Scientific reports, Vol. 6 (May 2016) , article 25663, ISSN 2045-2322

DOI: 10.1038/srep25663
PMID: 27174644


13 p, 2.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Neurociències (INc)
Articles > Research articles
Articles > Published articles

 Record created 2016-07-08, last modified 2024-03-28



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