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

Laflamme, Nathalie; Cisbani, Giulia; Préfontaine, Paul; Srour, Younes; Bernier, Jordan; St‐Pierre, Marie‐Kim; Tremblay, Marie‐Ève; Rivest, Serge

doi:10.3389/fncel.2018.00178

Cited by 45 publications

(46 citation statements)

References 70 publications

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“…Recently, cuprizone-mediated demyelination was shown to be alleviated in mice lacking microglial SIRPα that have increased numbers of CD11c+ microglia, pointing to their protective role (89). In line with the induction of CD11c+ microglia (81), stimulation of CSF1R ameliorated cuprizone-induced demyelination (146).…”

Section: Multiple Sclerosismentioning

confidence: 97%

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

2020

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Microglial heterogeneity has been the topic of much discussion in the scientific community. Elucidation of their plasticity and adaptability to disease states triggered early efforts to characterize microglial subsets. Over time, their phenotypes, and later on their homeostatic signature, were revealed, through the use of increasingly advanced transcriptomic techniques. Recently, an increasing number of these "microglial signatures" have been reported in various homeostatic and disease contexts. Remarkably, many of these states show similar overlapping microglial gene expression patterns, both in homeostasis and in disease or injury. In this review, we integrate information from these studies, and we propose a unique subset, for which we introduce a core signature, based on our own research and reports from the literature. We describe that this subset is found in development and in normal aging as well as in diverse diseases. We discuss the functions of this subset as well as how it is induced.

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Section: Multiple Sclerosismentioning

confidence: 97%

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

2020

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“…Microglia and CSF1R signaling pathway are involved in different neuroprotective roles, such as clearing myelin debris and toxic proteins from the cerebral environment. In this regard, modulation of the receptor is thought to be a novel therapeutic avenue for diseases, such as Alzheimer's disease (AD), multiple sclerosis (MS), and brain tumors (2,(4)(5)(6)(7). To better understand how CSF1R drives proliferation of microglial cells, we have deleted this receptor specifically in CX3CR1-postive cells in different nerve damage and pathologic models.…”

Section: Introductionmentioning

confidence: 99%

Role of Macrophage Colony-Stimulating Factor Receptor on the Proliferation and Survival of Microglia Following Systemic Nerve and Cuprizone-Induced Injuries

et al. 2020

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Microglia are the innate immune cells of the CNS and their proliferation, activation, and survival have previously been shown to be highly dependent on macrophage colony-stimulating factor receptor (CSF1R). Here we investigated the impact of the receptor in such processes using two different models of nerve injuries, namely hypoglossal axotomy and cuprizone-induced demyelination. Both models are associated with a robust microgliosis. The role of CSF1R was investigated using the gene deletion Cre/Lox system, which allows the conditional knockout following tamoxifen administration. We found that after 5 weeks of cuprizone diet that CSF1R suppression caused a significant impairment of microglia function. A reduced microgliosis was detected in the corpus collosum of CSF1R knockout mice compared to controls. In contrast to cuprizone model, the overall number of Iba1 cells was unchanged at all the times evaluated following hypoglossal axotomy in WT and cKO conditions. After nerve lesion, a tremendous proliferation was noticed in the ipsilateral hypoglossal nucleus to a similar level in both knockout and wild-type groups. We also observed infiltration of bone-marrow derived cells specifically in CSF1R-deficient mice, these cells tend to compensate the CSF1R signaling pathway suppression in resident microglia. Taking together our results suggest a different role of CSF1R in microglia depending on the model. In the pathologic context of cuprizone-induced demyelination CSF1R signaling pathway is essential to trigger proliferation and survival of microglia, while this is not the case in a model of systemic nerve injury. M-CSF/CSF1R is consequently not the unique system involved in microgliosis following nerve damages.

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“…One of the first papers providing evidence that increased recruitment of microglia/macrophages can support remyelination, regarded the anti-fungal amphotericin B and its association with macrophage colony-stimulating factor (M-CSF). Although using amphotericin B is precluded by its ability to stimulate TNF secretion and its toxic properties (Doring et al, 2015), the increased uptake of myelin debris induced by M-CSF in the cuprizone model remains interesting (Laflamme et al, 2018). The adoptive transfer of bone-marrow-derived M2 macrophages results in a shift of the immunological response from helper T1 to helper T2 lymphocytes through the production of anti-inflammatory cytokines, which in turn induces the polarization of microglia/macrophages to the M2 phenotype in a model of spinal cord injury (Ma et al, 2015).…”

Section: Therapeutic Modulation Of Microglia/macrophagesmentioning

confidence: 99%

Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions

Traiffort

Kassoussi

Zahaf

et al. 2020

Front. Cell. Neurosci.

139

108

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Myelination is an essential process that consists of the ensheathment of axons by myelin. In the central nervous system (CNS), myelin is synthesized by oligodendrocytes. The proliferation, migration, and differentiation of oligodendrocyte precursor cells constitute a prerequisite before mature oligodendrocytes extend their processes around the axons and progressively generate a multilamellar lipidic sheath. Although myelination is predominately driven by oligodendrocytes, the other glial cells including astrocytes and microglia, also contribute to this process. The present review is an update of the most recent emerging mechanisms involving astrocyte and microglia in myelin production. The contribution of these cells will be first described during developmental myelination that occurs in the early postnatal period and is critical for the proper development of cognition and behavior. Then, we will report the novel findings regarding the beneficial or deleterious effects of astroglia and microglia, which respectively promote or impair the endogenous capacity of oligodendrocyte progenitor cells (OPCs) to induce spontaneous remyelination after myelin loss. Acute delineation of astrocyte and microglia activities and cross-talk should uncover the way towards novel therapeutic perspectives aimed at recovering proper myelination during development or at breaking down the barriers impeding the regeneration of the damaged myelin that occurs in CNS demyelinating diseases.

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

Cited by 45 publications

References 70 publications

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies

Role of Macrophage Colony-Stimulating Factor Receptor on the Proliferation and Survival of Microglia Following Systemic Nerve and Cuprizone-Induced Injuries

Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions

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