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Csf1r microglia

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https://www.readbyqxmd.com/read/27859676/microglia-and-brain-macrophages-an-update
#1
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
#2
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
#3
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...
October 17, 2016: JAMA Neurology
https://www.readbyqxmd.com/read/27516055/elimination-of-microglia-improves-cognitive-function-following-cranial-irradiation
#4
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...
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/26348580/dynamic-microglial-modulation-of-spatial-learning-and-social-behavior
#13
Luisa Torres, Joan Danver, Kyungmin Ji, Jeremy T Miyauchi, Danling Chen, Maria E Anderson, Brian L West, John K Robinson, Stella E Tsirka
Microglia are active players in inflammation, but also have important supporting roles in CNS maintenance and function, including modulation of neuronal activity. We previously observed an increase in the frequency of excitatory postsynaptic current in organotypic brain slices after depletion of microglia using clodronate. Here, we describe that local hippocampal depletion of microglia by clodronate alters performance in tests of spatial memory and sociability. Global depletion of microglia by high-dose oral administration of a Csf1R inhibitor transiently altered spatial memory but produced no change in sociability behavior...
July 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/26232154/colony-stimulating-factor-1-receptor-inhibition-prevents-microglial-plaque-association-and-improves-cognition-in-3xtg-ad-mice
#14
Nabil N Dagher, Allison R Najafi, Kara M Neely Kayala, Monica R P Elmore, Terra E White, Rodrigo Medeiros, Brian L West, Kim N Green
BACKGROUND: Microglia are dependent upon colony-stimulating factor 1 receptor (CSF1R) signaling for their survival in the adult brain, with administration of the dual CSF1R/c-kit inhibitor PLX3397 leading to the near-complete elimination of all microglia brainwide. Here, we determined the dose-dependent effects of a specific CSF1R inhibitor (PLX5622) on microglia in both wild-type and the 3xTg-AD mouse model of Alzheimer's disease. METHODS: Wild-type mice were treated with PLX5622 for up to 21 days, and the effects on microglial numbers were assessed...
2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/26156998/elimination-of-microglia-improves-functional-outcomes-following-extensive-neuronal-loss-in-the-hippocampus
#15
Rachel A Rice, Elizabeth E Spangenberg, Hana Yamate-Morgan, Rafael J Lee, Rajan P S Arora, Michael X Hernandez, Andrea J Tenner, Brian L West, Kim N Green
UNLABELLED: With severe injury or disease, microglia become chronically activated and damage the local brain environment, likely contributing to cognitive decline. We previously discovered that microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for survival in the healthy adult brain, and we have exploited this dependence to determine whether such activated microglia contribute deleteriously to functional recovery following a neuronal lesion. Here, we induced a hippocampal lesion in mice for 25 d via neuronal expression of diphtheria toxin A-chain, producing both a neuroinflammatory reaction and behavioral alterations...
July 8, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26141825/common-neuropathological-features-underlie-distinct-clinical-presentations-in-three-siblings-with-hereditary-diffuse-leukoencephalopathy-with-spheroids-caused-by-csf1r-p-arg782his
#16
John L Robinson, EunRan Suh, Elisabeth M Wood, Edward B Lee, H Branch Coslett, Kevin Raible, Virginia M-Y Lee, John Q Trojanowski, Vivianna M Van Deerlin
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) presents with a variety of clinical phenotypes including motor impairments such as gait dysfunction, rigidity, tremor and bradykinesia as well as cognitive deficits including personality changes and dementia. In recent years, colony stimulating factor 1 receptor gene (CSF1R) has been identified as the primary genetic cause of HDLS. We describe the clinical and neuropathological features in three siblings with HDLS and the CSF1R p.Arg782His (c.2345G > A) pathogenic mutation...
2015: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/25975230/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia-caused-by-a-novel-r782g-mutation-in-csf1r
#17
Nicola Foulds, Reuben J Pengelly, Simon R Hammans, James A R Nicoll, David W Ellison, Adam Ditchfield, Sarah Beck, Sarah Ennis
We report a new family with autosomal dominant inheritance of a late onset rapidly progressive leukodystrophy in which exome sequencing has revealed a novel mutation p.R782G in the Colony-Stimulating Factor 1 Receptor gene (CSF1R). Neuropathology of two affected family members showed cerebral white matter degeneration with axonal swellings and pigmented macrophages. The few recently reported families with CSF1R mutations had been previously labelled "hereditary diffuse leukencephalopathy with axonal spheroids" (HDLS) and "pigmentary orthochromatic leukodystrophy" (POLD), disorders which now appear to form a disease continuum...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25849463/characterizing-newly-repopulated-microglia-in-the-adult-mouse-impacts-on-animal-behavior-cell-morphology-and-neuroinflammation
#18
Monica R P Elmore, Rafael J Lee, Brian L West, Kim N Green
Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS) resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored...
2015: PloS One
https://www.readbyqxmd.com/read/25672734/-neuropathology-of-hereditary-diffuse-leukoencephalopathy-with-axonal-spheroids-hdls
#19
REVIEW
Kiyomitsu Oyanagi
Hereditary diffuse leukoenchephalopathy with axonal spheroids (HDLS) is a disease showing progressive dementia and convulsion in humans at the age around 40's. HDLS usually shows autosomal dominant inheritance, but frequently has de novo occurrence. The causative gene is reported to be a gene encoding the colony stimulating factor 1 receptor (CSF1R). Neuropathological examination reveals severe loss of axons with axonal spheroids in the cerebral white matter. Microglia and astrocytes are upregulated in the lesions...
2014: Rinshō Shinkeigaku, Clinical Neurology
https://www.readbyqxmd.com/read/25574134/a-comprehensive-profile-of-chip-seq-based-pu-1-spi1-target-genes-in-microglia
#20
Jun-Ichi Satoh, Naohiro Asahina, Shouta Kitano, Yoshihiro Kino
Microglia are resident mononuclear phagocytes that play a principal role in the maintenance of normal tissue homeostasis in the central nervous system (CNS). Microglia, rapidly activated in response to proinflammatory stimuli, are accumulated in brain lesions of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. The E26 transformation-specific (ETS) family transcription factor PU.1/Spi1 acts as a master regulator of myeloid and lymphoid development. PU.1-deficient mice show a complete loss of microglia, indicating that PU...
2014: Gene Regulation and Systems Biology
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