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Csf1r microglia

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https://www.readbyqxmd.com/read/28539419/microglia-are-irrelevant-for-neuronal-degeneration-and-axon-regeneration-after-acute-injury
#1
Alexander M Hilla, Heike Diekmann, Dietmar Fischer
The role of microglia in de- and regenerative processes after damage of the nervous system still remains ambiguous, partially due to the paucity of appropriate investigative methods. Here, we show that treatment with the pharmacological colony stimulating factor 1 receptor inhibitor PLX5622 specifically eliminated microglia in murine retinae and optic nerves. Interestingly, time course and extent of retinal ganglion cell (RGC) degeneration after optic nerve crush remained unaffected upon microglia depletion, although remnants of pre-labeled apoptotic RGCs were not cleared from the retina in these animals...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28427424/microglial-depletion-alters-the-brain-neuroimmune-response-to-acute-binge-ethanol-withdrawal
#2
T Jordan Walter, Fulton T Crews
BACKGROUND: Recent studies have implicated microglia-the resident immune cells of the brain-in the pathophysiology of alcoholism. Indeed, post-mortem alcoholic brains show increased microglial markers and increased immune gene expression; however, the effects of ethanol on microglial functioning and how this impacts the brain remain unclear. In this present study, we investigate the effects of acute binge ethanol on microglia and how microglial depletion changes the brain neuroimmune response to acute binge ethanol withdrawal...
April 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28405620/microglia-mediate-postoperative-hippocampal-inflammation-and-cognitive-decline-in-mice
#3
Xiaomei Feng, Martin Valdearcos, Yosuke Uchida, David Lutrin, Mervyn Maze, Suneil K Koliwad
Surgery can induce cognitive decline, a risk that increases with advancing age. In rodents, postoperative cognitive decline (POCD) is associated with the inflammatory activation of hippocampal microglia. To examine the role of microglia in POCD, we inhibited the colony-stimulating factor 1 receptor (CSF1R) in adult mice, effectively depleting CNS microglia. Surgical trauma (tibial fracture) reduced the ability of mice to remember a conditioned response learned preoperatively, a deficit more pronounced and persistent in mice with diet-induced obesity (DIO)...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28373688/microglial-recruitment-of-il-1%C3%AE-producing-monocytes-to-brain-endothelium-causes-stress-induced-anxiety
#4
D B McKim, M D Weber, A Niraula, C M Sawicki, X Liu, B L Jarrett, K Ramirez-Chan, Y Wang, R M Roeth, A D Sucaldito, C G Sobol, N Quan, J F Sheridan, J P Godbout
Psychosocial stress contributes to the development of anxiety and depression. Recent clinical studies have reported increased inflammatory leukocytes in circulation of individuals with stress-related psychiatric disorders. Parallel to this, our work in mice shows that social stress causes release of inflammatory monocytes into circulation. In addition, social stress caused the development of prolonged anxiety that was dependent on inflammatory monocytes in the brain. Therefore, we hypothesize that chronic stress drives the production of inflammatory monocytes that are actively recruited to the brain by microglia, and these monocytes augment neuroinflammatory signaling and prolong anxiety...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28286294/specific-suppression-of-microgliosis-cannot-circumvent-the-severe-neuropathology-in-peroxisomal-%C3%AE-oxidation-deficient-mice
#5
L Beckers, S Stroobants, S Verheijden, B West, R D'Hooge, M Baes
An important hallmark of various neurodegenerative disorders is the proliferation and activation of microglial cells, the resident immune cells of the central nervous system (CNS). Mice that lack multifunctional protein-2 (MFP2), the key enzyme in peroxisomal β-oxidation, develop excessive microgliosis that positively correlates with behavioral deficits whereas no neuronal loss occurs. However, the precise contribution of neuroinflammation to the fatal neuropathology of MFP2 deficiency remains largely unknown...
March 7, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28273719/depletion-of-microglia-exacerbates-postischemic-inflammation-and-brain-injury
#6
Wei-Na Jin, Samuel Xiang-Yu Shi, Zhiguo Li, Minshu Li, Kristofer Wood, Rayna J Gonzales, Qiang Liu
Brain ischemia elicits microglial activation and microglia survival depend on signaling through colony-stimulating factor 1 receptor (CSF1R). Although depletion of microglia has been linked to worse stroke outcomes, it remains unclear to what extent and by what mechanisms activated microglia influence ischemia-induced inflammation and injury in the brain. Using a mouse model of transient focal cerebral ischemia and reperfusion, we demonstrated that depletion of microglia via administration of the dual CSF1R/c-Kit inhibitor PLX3397 exacerbates neurodeficits and brain infarction...
June 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28251674/microglial-repopulation-resolves-inflammation-and-promotes-brain-recovery-after-injury
#7
Rachel A Rice, Jason Pham, Rafael J Lee, Allison R Najafi, Brian L West, Kim N Green
Microglia mediate chronic neuroinflammation following central nervous system (CNS) disease or injury, and in doing so, damage the local brain environment by impairing recovery and contributing to disease processes. Microglia are critically dependent on signaling through the colony-stimulating factor 1 receptor (CSF1R) and can be eliminated via administration of CSF1R inhibitors. Resolving chronic neuroinflammation represents a universal goal for CNS disorders, but long-term microglial elimination may not be amenable to clinical use...
June 2017: Glia
https://www.readbyqxmd.com/read/28236968/regulation-of-embryonic-and-postnatal-development-by-the-csf-1-receptor
#8
REVIEW
Violeta Chitu, E Richard Stanley
Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/27859676/microglia-and-brain-macrophages-an-update
#9
REVIEW
Atsushi Sasaki
Current immunohistochemical techniques have made the identification of microglia possible in routinely processed tissue sections from human brains. Previous studies have indicated that almost no neurological diseases exist without microglial activation. Activated microglia often secrete inflammatory cytokines in various diseases, including Alzheimer's disease, but microglial activation is not always associated with inflammation. The equation microglial activation means "neuroinflammation" is absurd and misleading...
November 18, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/27776109/sall1-is-a-transcriptional-regulator-defining-microglia-identity-and-function
#10
Anne Buttgereit, Iva Lelios, Xueyang Yu, Melissa Vrohlings, Natalie R Krakoski, Emmanuel L Gautier, Ryuichi Nishinakamura, Burkhard Becher, Melanie Greter
Microglia are the resident macrophages of the central nervous system (CNS). Gene expression profiling has identified Sall1, which encodes a transcriptional regulator, as a microglial signature gene. We found that Sall1 was expressed by microglia but not by other members of the mononuclear phagocyte system or by other CNS-resident cells. Using Sall1 for microglia-specific gene targeting, we found that the cytokine receptor CSF1R was involved in the maintenance of adult microglia and that the receptor for the cytokine TGF-β suppressed activation of microglia...
December 2016: Nature Immunology
https://www.readbyqxmd.com/read/27749956/analysis-of-mutations-in-aars2-in-a-series-of-csf1r-negative-patients-with-adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia
#11
David S Lynch, Wei Jia Zhang, Rahul Lakshmanan, Justin A Kinsella, Günes Altiokka Uzun, Merih Karbay, Zeynep Tüfekçioglu, Hasmet Hanagasi, Georgina Burke, Nicola Foulds, Simon R Hammans, Anupam Bhattacharjee, Heather Wilson, Matthew Adams, Mark Walker, James A R Nicoll, Jeremy Chataway, Nick Fox, Indran Davagnanam, Rahul Phadke, Henry Houlden
Importance: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a frequent cause of adult-onset leukodystrophy known to be caused by autosomal dominant mutations in the CSF1R (colony-stimulating factor 1) gene. The discovery that CSF1R mutations cause ALSP led to more accurate prognosis and genetic counseling for these patients in addition to increased interest in microglia as a target in neurodegeneration. However, it has been known since the discovery of the CSF1R gene that there are patients with typical clinical and radiologic evidence of ALSP who do not carry pathogenic CSF1R mutations...
December 1, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27516055/elimination-of-microglia-improves-cognitive-function-following-cranial-irradiation
#12
Munjal M Acharya, Kim N Green, Barrett D Allen, Allison R Najafi, Amber Syage, Harutyun Minasyan, Mi T Le, Takumi Kawashita, Erich Giedzinski, Vipan K Parihar, Brian L West, Janet E Baulch, Charles L Limoli
Cranial irradiation for the treatment of brain cancer elicits progressive and severe cognitive dysfunction that is associated with significant neuropathology. Radiation injury in the CNS has been linked to persistent microglial activation, and we find upregulation of pro-inflammatory genes even 6 weeks after irradiation. We hypothesize that depletion of microglia in the irradiated brain would have a neuroprotective effect. Adult mice received acute head only irradiation (9 Gy) and were administered a dietary inhibitor (PLX5622) of colony stimulating factor-1 receptor (CSF1R) to deplete microglia post-irradiation...
August 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27423618/a-family-with-hereditary-diffuse-leukoencephalopathy-with-spheroids-caused-by-a-novel-c-2442-2t-c-mutation-in-the-csf1r-gene
#13
Ito Kawakami, Eizo Iseki, Koji Kasanuki, Michiko Minegishi, Kiyoshi Sato, Hiroyuki Hino, Katsuhiko Shibuya, Kohshiro Fujisawa, Shinji Higashi, Haruhiko Akiyama, Akiko Furuta, Masashi Takanashi, Yuanzhe Li, Nobutaka Hattori, Yoshio Mitsuyama, Heii Arai
Clinical phenotypes of hereditary diffuse leukoencephalopathy with spheroids (HDLS), a familial progressive neurodegenerative disorder affecting the white matter of the brain, are heterogenous and may include behavioral and personality changes, memory impairment, parkinsonism, seizure, and spasticity. Thus, HDLS is frequently unrecognized and misdiagnosed. Heterozygous mutations located within the kinase domain of the gene encoding the colony-stimulating factor 1 receptor (CSF1R), a cell surface receptor with key roles in development and innate immunity, have been shown in HDLS...
August 15, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27338940/hereditary-diffuse-leukoencephalopathy-with-axonal-spheroids-hdls-update-on-molecular-genetics
#14
REVIEW
Carmen Stabile, Ilaria Taglia, Carla Battisti, Silvia Bianchi, Antonio Federico
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a rare autosomal dominant disease characterized by giant neuroaxonal swellings (spheroids) within the cerebral white matter (WM). Symptoms are variable and can include cognitive, mental and motor dysfunctions. Patients carry mutations in the protein kinase domain of the colony-stimulating factor 1 receptor (CSF1R) which is a tyrosine kinase receptor essential for microglia development. To date, more than 50 pathogenic variants have been reported in patients with HDLS, including missense, frameshift and non-sense mutations, but also deletions and splice-site mutations, all located in the intracellular tyrosine kinase domain, encoded by exons 12-22...
September 2016: Neurological Sciences
https://www.readbyqxmd.com/read/27132056/neurons-and-astroglia-govern-microglial-endotoxin-tolerance-through-macrophage-colony-stimulating-factor-receptor-mediated-erk1-2-signals
#15
Chun-Hsien Chu, Shijun Wang, Chia-Ling Li, Shih-Heng Chen, Chih-Fen Hu, Yi-Lun Chung, Shiou-Lan Chen, Qingshan Wang, Ru-Band Lu, Hui-Ming Gao, Jau-Shyong Hong
Endotoxin tolerance (ET) is a reduced responsiveness of innate immune cells like macrophages/monocytes to an endotoxin challenge following a previous encounter with the endotoxin. Although ET in peripheral systems has been well studied, little is known about ET in the brain. The present study showed that brain immune cells, microglia, being different from peripheral macrophages, displayed non-cell autonomous mechanisms in ET formation. Specifically, neurons and astroglia were indispensable for microglial ET...
July 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27013192/csf1-overexpression-promotes-high-grade-glioma-formation-without-impacting-the-polarization-status-of-glioma-associated-microglia-and-macrophages
#16
Ishani De, Megan D Steffen, Paul A Clark, Clayton J Patros, Emily Sokn, Stephanie M Bishop, Suzanne Litscher, Vilena I Maklakova, John S Kuo, Fausto J Rodriguez, Lara S Collier
Current therapies for high-grade gliomas extend survival only modestly. The glioma microenvironment, including glioma-associated microglia/macrophages (GAM), is a potential therapeutic target. The microglia/macrophage cytokine CSF1 and its receptor CSF1R are overexpressed in human high-grade gliomas. To determine whether the other known CSF1R ligand IL34 is expressed in gliomas, we examined expression array data of human high-grade gliomas and performed RT-PCR on glioblastoma sphere-forming cell lines (GSC)...
May 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/26921617/eliminating-microglia-in-alzheimer-s-mice-prevents-neuronal-loss-without-modulating-amyloid-%C3%AE-pathology
#17
Elizabeth E Spangenberg, Rafael J Lee, Allison R Najafi, Rachel A Rice, Monica R P Elmore, Mathew Blurton-Jones, Brian L West, Kim N Green
In addition to amyloid-β plaque and tau neurofibrillary tangle deposition, neuroinflammation is considered a key feature of Alzheimer's disease pathology. Inflammation in Alzheimer's disease is characterized by the presence of reactive astrocytes and activated microglia surrounding amyloid plaques, implicating their role in disease pathogenesis. Microglia in the healthy adult mouse depend on colony-stimulating factor 1 receptor (CSF1R) signalling for survival, and pharmacological inhibition of this receptor results in rapid elimination of nearly all of the microglia in the central nervous system...
April 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/26642091/injured-sensory-neuron-derived-csf1-induces-microglial-proliferation-and-dap12-dependent-pain
#18
Zhonghui Guan, Julia A Kuhn, Xidao Wang, Bradley Colquitt, Carlos Solorzano, Smitha Vaman, Andrew K Guan, Zoe Evans-Reinsch, Joao Braz, Marshall Devor, Sherry L Abboud-Werner, Lewis L Lanier, Stavros Lomvardas, Allan I Basbaum
Although microglia have been implicated in nerve injury-induced neuropathic pain, the manner by which injured sensory neurons engage microglia remains unclear. We found that peripheral nerve injury induced de novo expression of colony-stimulating factor 1 (CSF1) in injured sensory neurons. CSF1 was transported to the spinal cord, where it targeted the microglial CSF1 receptor (CSF1R). Cre-mediated sensory neuron deletion of Csf1 completely prevented nerve injury-induced mechanical hypersensitivity and reduced microglial activation and proliferation...
January 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/26541819/microglia-regulate-hippocampal-neurogenesis-during-chronic-neurodegeneration
#19
Chiara De Lucia, Adeline Rinchon, Adrian Olmos-Alonso, Kristoffer Riecken, Boris Fehse, Delphine Boche, V Hugh Perry, Diego Gomez-Nicola
Neurogenesis is altered in neurodegenerative disorders, partly regulated by inflammatory factors. We have investigated whether microglia, the innate immune brain cells, regulate hippocampal neurogenesis in neurodegeneration. Using the ME7 model of prion disease we applied gain- or loss-of CSF1R function, as means to stimulate or inhibit microglial proliferation, respectively, to dissect the contribution of these cells to neurogenesis. We found that increased hippocampal neurogenesis correlates with the expansion of the microglia population...
July 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/26449250/orally-administered-colony-stimulating-factor-1-receptor-inhibitor-plx3397-in-recurrent-glioblastoma-an-ivy-foundation-early-phase-clinical-trials-consortium-phase-ii-study
#20
MULTICENTER STUDY
Nicholas Butowski, Howard Colman, John F De Groot, Antonio M Omuro, Lakshmi Nayak, Patrick Y Wen, Timothy F Cloughesy, Adhirai Marimuthu, Sam Haidar, Arie Perry, Jason Huse, Joanna Phillips, Brian L West, Keith B Nolop, Henry H Hsu, Keith L Ligon, Annette M Molinaro, Michael Prados
BACKGROUND: The colony stimulating factor 1 receptor (CSF1R) ligands, CSF1 and interleukin-34, and the KIT ligand, stem cell factor, are expressed in glioblastoma (GB). Microglia, macrophages, blood vessels, and tumor cells also express CSF1R, and depletion of the microglia reduces tumor burden and invasive capacity. PLX3397 is an oral, small molecule that selectively inhibits CSF1R and KIT, penetrates the blood-brain barrier in model systems, and represents a novel approach for clinical development...
April 2016: Neuro-oncology
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