scholarly journals G-CSF (Granulocyte-Colony Stimulating Factor) in the Central Nervous System

Cell Cycle ◽  
2005 ◽  
Vol 4 (12) ◽  
pp. 1753-1757 ◽  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
The Central Nervous System ◽  
Stimulating Factor

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals Microglia: Same same, but different

2019 ◽  
Vol 216 (10) ◽  
pp. 2223-2225 ◽  
Author(s):  
Katrin Kierdorf ◽  
Marco Prinz
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Social Behavior ◽  
Motor Function ◽  
Colony Stimulating Factor ◽  
The Central Nervous System ◽  
Stimulating Factor

Microglial identity in the central nervous system (CNS) is dependent on colony stimulating factor 1 receptor (CSF-1R) signaling and its ligands IL-34 and colony stimulating factor 1 (CSF-1). In this issue of JEM, Kana et al. (https://doi.org/10.1084/jem.20182037) make the important discovery that CSF-1, but not IL-34, orchestrates cerebellar microglial homeostasis in mice, and its deficiency resulted in severe cerebellar dysfunctions accompanied by defects in motor function and social behavior.

scholarly journals Permanent neuroglial remodeling of the retina following infiltration of CSF1R inhibition-resistant peripheral monocytes

2018 ◽  
Vol 115 (48) ◽  
pp. E11359-E11368 ◽  
Author(s):  
Eleftherios I. Paschalis ◽  
Fengyang Lei ◽  
Chengxin Zhou ◽  
Vassiliki Kapoulea ◽  
Reza Dana ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Bone Marrow ◽  
Nervous System ◽  
Ocular Injury ◽  
Colony Stimulating Factor ◽  
Mhc Ii ◽  
Tnf Α ◽  
The Central Nervous System ◽  
Stimulating Factor

Previous studies have demonstrated that ocular injury can lead to prompt infiltration of bone-marrow–derived peripheral monocytes into the retina. However, the ability of these cells to integrate into the tissue and become microglia has not been investigated. Here we show that such peripheral monocytes that infiltrate into the retina after ocular injury engraft permanently, migrate to the three distinct microglia strata, and adopt a microglia-like morphology. In the absence of ocular injury, peripheral monocytes that repopulate the retina after depletion with colony-stimulating factor 1 receptor (CSF1R) inhibitor remain sensitive to CSF1R inhibition and can be redepleted. Strikingly, consequent to ocular injury, the engrafted peripheral monocytes are resistant to depletion by CSF1R inhibitor and likely express low CSF1R. Moreover, these engrafted monocytes remain proinflammatory, expressing high levels of MHC-II, IL-1β, and TNF-α over the long term. The observed permanent neuroglia remodeling after injury constitutes a major immunological change that may contribute to progressive retinal degeneration. These findings may also be relevant to other degenerative conditions of the retina and the central nervous system.

scholarly journals A csf1rb mutation uncouples two waves of microglia development in zebrafish

Development ◽  
2020 ◽  
pp. dev.194241
Author(s):  
Giuliano Ferrero ◽  
Magali Miserocchi ◽  
Elodie Di Ruggiero ◽  
Valérie Wittamer
Keyword(s):  
Central Nervous System ◽  
Adult Population ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Mapping Strategy ◽  
The Central Nervous System ◽  
Evolutionary Aspects ◽  
Stimulating Factor ◽  
Specific Contribution

In vertebrates, the ontogeny of microglia, the resident macrophages of the central nervous system, initiates early during development from primitive macrophages. While murine embryonic microglia then persist through life, in zebrafish these cells are transient, as they are fully replaced by an adult population originating from larval hematopoietic stem cell (HSC)-derived progenitors. Colony-stimulating factor receptor 1 (csf1r) is a fundamental regulator of microglia ontogeny in vertebrates, including zebrafish which possess two paralogous genes: csf1ra and csf1rb. While previous work showed mutation in both genes completely abrogates microglia development, the specific contribution of each paralog remains largely unknown. Here, using a fate-mapping strategy to discriminate between the two microglial waves, we uncover non-overlapping roles for csf1ra and csf1rb in hematopoiesis, and identified csf1rb as an essential regulator of adult microglia development. Notably, we demonstrate that csf1rb positively regulates HSC-derived myelopoiesis, resulting in macrophage deficiency, including microglia, in adult mutant animals. Overall, this study contributes to new insights into evolutionary aspects of Csf1r signaling and provides an unprecedented framework for the functional dissection of embryonic versus adult microglia in vivo.

Granulocyte Colony-Stimulating Factor (G-CSF) Stimulates Sympathetic Nervous System Activity in the Bone Marrow

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2419-2419 ◽  
Author(s):  
Michela Battista ◽  
Simon Mendez-Ferrer ◽  
Paul S. Frenette
Keyword(s):  
Bone Marrow ◽  
Nervous System ◽  
Plasma Membrane ◽  
Sympathetic Nervous System ◽  
Lipid Rafts ◽  
Synaptic Cleft ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Sympathetic Nervous ◽  
Stimulating Factor

Abstract Granulocyte colony-stimulating factor (G-CSF) is the agent most commonly used clinically to elicit hematopoietic stem and progenitor cells (HSPCs) mobilization from the bone marrow (BM) to the peripheral blood. Our previous studies indicate the sympathetic nervous system (SNS) controls G-CSF-induced HSPCs egress from the BM and that G-CSF decreases catecholamine levels in bone/BM tissues (Cell2006; 124:407). However the molecular basis for this depletion is unknown. Here we show that G-CSF stimulates selectively the activity of the SNS in bone/BM microenvironment in mice. Norepinephrine (NE), a catecholamine and the principal neurotransmitter of the SNS, is synthesized by the rate-limiting enzyme tyrosine hydroxylase (TH). Since TH is a catecholaminergic marker which reflects the extent of sympathetic innervation, we evaluated its expression in bone/BM tissues after G-CSF treatment. TH immunofluorescence staining analysis in longitudinal frozen sections of femurs exhibited a strong punctuate staining of the catecholamine-producing enzyme that was increased 10-fold in G-CSF-treated mice compared to control animals. This result was also confirmed by Western blot analysis of equal amount of protein obtained from BM lysates of G-CSF-treated and control animals. Because NE release and removal from the extracellular space determine tissue NE turnover and regulate the sympathetic activation, we evaluated NE release and uptake in sympathetic cervical ganglia (SCG) in organ cultures treated with G-CSF. Although the release of [3H]NE from cultured ganglia was not affected by G-CSF, we found a significant reduction in the reuptake rate. NE clearance from the synaptic cleft is mediated by the Na+-dependent NE transporter (NET). NET is selectively expressed and localized in lipid rafts of the plasma membrane of the noradrenergic nerve terminals and it is internalized as a result of its down-regulation. We thus isolated lipid rafts from BM homogenized in lysis buffer containing 1% Triton X-100 and subjected to sucrose gradient centrifugation. We found that G-CSF induced the redistribution of NET from the plasma membrane as revealed by a strong reduction of NET levels in BM lipid raft-enriched gradient fractions and by an increase of NET levels in BM non-raft fractions following G-CSF treatment. Moreover Q-PCR analysis of catecholamine-inactivating enzymes revealed reduced mRNA levels of the monoamine oxidase (MAO) and the catechol-O-methyltransferase (COMT) enzymes derived from BM of mice injected with G-CSF compared to untreated animals. Altogether, these results demonstrate that G-CSF treatment affects NE turnover impairing the removal of NE from the synaptic cleft and therefore leading to an increase of the concentration of the extracellular NE. A likely consequence is a prolongation of the postsynaptic action of NE on its receptors and ultimately an augmented sympathetic activity in the bone marrow microenvironment.

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