Colony‐stimulating factor‐1 receptor inhibition attenuates microgliosis and myelin loss but exacerbates neurodegeneration in the chronic cuprizone model

2021 ◽  
Author(s):  
V.S.B. Wies Mancini ◽  
A.A. Di Pietro ◽  
S. de Olmos ◽  
P.R. Silva ◽  
M. Vence ◽  
...  
Keyword(s):  
Colony Stimulating Factor ◽  
Receptor Inhibition ◽  
Stimulating Factor

scholarly journals Colony-stimulating factor 1 receptor inhibition prevents against lipopolysaccharide -induced osteoporosis by inhibiting osteoclast formation

2019 ◽  
Vol 115 ◽  
pp. 108916 ◽  
Author(s):  
Xin-fang Wang ◽  
Ya-juan Wang ◽  
Tong-ying Li ◽  
Jiang-xue Guo ◽  
Fang Lv ◽  
...  
Keyword(s):  
Osteoclast Formation ◽  
Colony Stimulating Factor ◽  
Receptor Inhibition ◽  
Stimulating Factor

Microglial modulation through colony-stimulating factor-1 receptor inhibition attenuates demyelination

Glia ◽  
2018 ◽  
Vol 67 (2) ◽  
pp. 291-308 ◽  
Author(s):  
Victoria Sofía Berenice Wies Mancini ◽  
Juana María Pasquini ◽  
Jorge Daniel Correale ◽  
Laura Andrea Pasquini
Keyword(s):  
Colony Stimulating Factor ◽  
Receptor Inhibition ◽  
Stimulating Factor

scholarly journals Colony stimulating factor 1 receptor inhibition eliminates microglia and attenuates brain injury after intracerebral hemorrhage

2016 ◽  
Vol 37 (7) ◽  
pp. 2383-2395 ◽  
Author(s):  
Minshu Li ◽  
Zhiguo Li ◽  
Honglei Ren ◽  
Wei-Na Jin ◽  
Kristofer Wood ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Autologous Blood ◽  
Lesion Size ◽  
Experimental Models ◽  
Colony Stimulating Factor ◽  
Receptor Inhibition ◽  
Experimental Mouse ◽  
The Brain ◽  
Stimulating Factor ◽  
Blood Brain Barrier Integrity

Microglia are the first responders to intracerebral hemorrhage, but their precise role in intracerebral hemorrhage remains to be defined. Microglia are the only type of brain cells expressing the colony-stimulating factor 1 receptor, a key regulator for myeloid lineage cells. Here, we determined the effects of a colony-stimulating factor 1 receptor inhibitor (PLX3397) on microglia and the outcome in the context of experimental mouse intracerebral hemorrhage. We show that PLX3397 effectively depleted microglia, and the depletion of microglia was sustained after intracerebral hemorrhage. Importantly, colony-stimulating factor 1 receptor inhibition attenuated neurodeficits and brain edema in two experimental models of intracerebral hemorrhage induced by injection of collagenase or autologous blood. The benefit of colony-stimulating factor 1 receptor inhibition was associated with reduced leukocyte infiltration in the brain and improved blood–brain barrier integrity after intracerebral hemorrhage, and each observation was independent of lesion size or hematoma volume. These results demonstrate that suppression of colony-stimulating factor 1 receptor signaling ablates microglia and confers protection after intracerebral hemorrhage.

scholarly journals Colony stimulating factor 1 receptor inhibition delays recurrence of glioblastoma after radiation by altering myeloid cell recruitment and polarization

2015 ◽  
Vol 18 (6) ◽  
pp. 797-806 ◽  
Author(s):  
Jason H. Stafford ◽  
Takahisa Hirai ◽  
Lei Deng ◽  
Sophia B. Chernikova ◽  
Kimiko Urata ◽  
...  
Keyword(s):  
Myeloid Cell ◽  
Colony Stimulating Factor ◽  
Cell Recruitment ◽  
Receptor Inhibition ◽  
Stimulating Factor

scholarly journals Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice

2015 ◽  
Vol 12 (1) ◽  
Author(s):  
Nabil N. Dagher ◽  
Allison R. Najafi ◽  
Kara M. Neely Kayala ◽  
Monica R. P. Elmore ◽  
Terra E. White ◽  
...  
Keyword(s):  
Colony Stimulating Factor ◽  
Receptor Inhibition ◽  
Stimulating Factor

scholarly journals CSF1R inhibition rescues tau pathology and neurodegeneration in an A/T/N model with combined AD pathologies, while preserving plaque associated microglia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Chritica Lodder ◽  
Isabelle Scheyltjens ◽  
Ilie Cosmin Stancu ◽  
Pablo Botella Lucena ◽  
Manuel Gutiérrez de Ravé ◽  
...  
Keyword(s):  
Neurofibrillary Tangles ◽  
Microglial Activation ◽  
Amyloid Plaques ◽  
Colony Stimulating Factor ◽  
Tau Pathology ◽  
Preclinical Models ◽  
Receptor Inhibition ◽  
Single Cell Rna Sequencing ◽  
The Brain ◽  
Stimulating Factor

AbstractAlzheimer's disease (AD) is characterized by a sequential progression of amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N), constituting ATN pathology. While microglia are considered key contributors to AD pathogenesis, their contribution in the combined presence of ATN pathologies remains incompletely understood. As sensors of the brain microenvironment, microglial phenotypes and contributions are importantly defined by the pathologies in the brain, indicating the need for their analysis in preclinical models that recapitulate combined ATN pathologies, besides their role in A and T models only. Here, we report a new tau-seed model in which amyloid pathology facilitates bilateral tau propagation associated with brain atrophy, thereby recapitulating robust ATN pathology. Single-cell RNA sequencing revealed that ATN pathology exacerbated microglial activation towards disease-associated microglia states, with a significant upregulation of Apoe as compared to amyloid-only models (A). Importantly, Colony-Stimulating Factor 1 Receptor inhibition preferentially eliminated non-plaque-associated versus plaque associated microglia. The preferential depletion of non-plaque-associated microglia significantly attenuated tau pathology and neuronal atrophy, indicating their detrimental role during ATN progression. Together, our data reveal the intricacies of microglial activation and their contributions to pathology in a model that recapitulates the combined ATN pathologies of AD. Our data may provide a basis for microglia-targeting therapies selectively targeting detrimental microglial populations, while conserving protective populations.

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