mCSF-Induced Microglial Activation Prevents Myelin Loss and Promotes Its Repair in a Mouse Model of Multiple Sclerosis

Frontiers in Cellular Neuroscience
Nathalie LaflammeSerge Rivest

Abstract

A pathological hallmark of multiple sclerosis (MS) is myelin loss in brain white matter accompanied by compromised remyelination. Demyelinated lesions are deeply associated with oligodendrocyte apoptosis and a robust inflammatory response. Although various studies point towards a noxious role of inflammation in MS, others emphasize a positive role for the innate immune cells in disease progression. A cytokine well-known to stimulate cell survival, proliferation and differentiation of myeloid cells, macrophage colony-stimulating factor (mCSF), was administered to mice during a 5 week-long cuprizone diet. Treated mice exhibited reduced myelin loss during the demyelination phase, together with an increased number of microglia and oligodendrocyte precursor cells in lesion sites. Tamoxifen-induced conditional deletion of the mCSF receptor in microglia from cuprizone-fed mice caused aberrant myelin debris accumulation in the corpus callosum and reduced microglial phagocytic response. mCSF therefore plays a key role in stimulating myelin clearance by the brain innate immune cells, which is a prerequisite for proper remyelination and myelin repair processes.

References

Jan 23, 1999·Journal of Neuroimmunology·M M HiremathGlenn K Matsushima
Jan 10, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nathalie Laflamme, Serge Rivest
Jan 18, 2002·The New England Journal of Medicine·Ansi ChangBruce D Trapp
Feb 15, 2002·Brain : a Journal of Neurology·Guus Wolswijk
Sep 13, 2002·Journal of Neuroimmunology·Eileen J McMahonGlenn K Matsushima
Aug 30, 2003·Brain Pathology·Mark F StidworthyRobin J M Franklin
Dec 11, 2003·Molecular and Cellular Neurosciences·Tamir Ben-HurNikolaos Grigoriadis
Mar 18, 2005·Annual Review of Immunology·P R TaylorS Gordon
Jan 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·M R KotterRobin J M Franklin
Feb 9, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Isaias GlezerSerge Rivest
Oct 31, 2006·Journal of Clinical Pathology·S Love
Apr 4, 2007·Journal of Neurochemistry·Kristina A KigerlPhillip G Popovich
Apr 5, 2007·European Journal of Immunology·Laura PiccioPaola Panina-Bordignon
Apr 26, 2007·The American Journal of Pathology·Leah T RemingtonTrevor Owens
Apr 27, 2007·Neuroscience·Isaias GlezerSerge Rivest
Oct 31, 2007·Journal of Magnetic Resonance Imaging : JMRI·Qi-Zhu WuGary F Egan
Nov 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Audrey BoivinSteve Lacroix
Apr 9, 2008·Journal of Neurology·Robin J M Franklin, M R Kotter
Jun 14, 2008·Nature Reviews. Immunology·John A Hamilton
Jun 24, 2008·Brain : a Journal of Neurology·H NeumannRobin J M Franklin
Jul 30, 2008·Methods in Enzymology·Antonella TinariWalter Malorni
Sep 8, 2010·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·V Wee Yong
Dec 22, 2010·The British Journal of Radiology·A FitsioriM I Vargas
Jun 21, 2012·Nature Reviews. Neuroscience·Peter K StysJeroen J G Geurts
May 28, 2013·Trends in Immunology·Sarah B SimmonsJoan M Goverman
Jul 11, 2013·Clinical & Developmental Immunology·Khalil S Rawji, V Wee Yong
Jul 23, 2013·Nature Neuroscience·Veronique E MironCharles Ffrench-Constant
Jan 8, 2014·Molecular Neurobiology·Ruying FuYamei Tang
Mar 25, 2014·Frontiers in Cellular Neuroscience·Viktoria GudiMartin Stangel

Citations

Mar 16, 2019·Cellular & Molecular Immunology·Heather Y F YongV Wee Yong
Apr 23, 2020·Frontiers in Immunology·Anouk Benmamar-BadelAgnieszka Wlodarczyk
Apr 23, 2020·Frontiers in Cellular Neuroscience·Elisabeth TraiffortYousra Laouarem
Jan 29, 2019·Frontiers in Cellular Neuroscience·Agnieszka WlodarczykTrevor Owens
Jul 1, 2019·Nature Reviews. Neurology·Amy F Lloyd, Veronique E Miron
Jan 9, 2019·Frontiers in Cellular Neuroscience·Vincent Pons, Serge Rivest
Jul 29, 2019·Journal of Neuroinflammation·Nicholas J WaskoRobert B Clark
Aug 28, 2020·Scandinavian Journal of Immunology·Trevor OwensReza Khorooshi
Jan 23, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Adham Fani MalekiSerge Rivest
Oct 31, 2020·Frontiers in Immunology·Igal Ifergan, Stephen D Miller
Nov 12, 2020·Frontiers in Cellular Neuroscience·Vincent Pons, Serge Rivest
Apr 16, 2021·Molecular Psychiatry·Giulia Cisbani, Serge Rivest

Methods Mentioned

BETA
electron microscopy
X-ray

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