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Marco Colonna, Oleg Butovsky
Microglia are resident cells of the brain that regulate brain development, maintenance of neuronal networks, and injury repair. Microglia serve as brain macrophages but are distinct from other tissue macrophages owing to their unique homeostatic phenotype and tight regulation by the central nervous system (CNS) microenvironment. They are responsible for the elimination of microbes, dead cells, redundant synapses, protein aggregates, and other particulate and soluble antigens that may endanger the CNS. Furthermore, as the primary source of proinflammatory cytokines, microglia are pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses...
February 9, 2017: Annual Review of Immunology
B Smith, J Whang, O Butovsky, J Scholz
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
Preet G S Makker, Samuel S Duffy, Justin G Lees, Chamini J Perera, Ryan S Tonkin, Oleg Butovsky, Susanna B Park, David Goldstein, Gila Moalem-Taylor
Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain is a debilitating adverse effect of cancer treatment. Current understanding of the mechanisms underpinning CIPN is limited and there are no effective treatment strategies. In this study, we treated male C57BL/6J mice with 4 cycles of either Paclitaxel (PTX) or Oxaliplatin (OXA) over a week and tested pain hypersensitivity and changes in peripheral immune responses and neuroinflammation on days 7 and 13 post 1st injection. We found that both PTX and OXA caused significant mechanical allodynia...
2017: PloS One
Eugene Drokhlyansky, Didem Göz Aytürk, Timothy K Soh, Ryan Chrenek, Elaine O'Loughlin, Charlotte Madore, Oleg Butovsky, Constance L Cepko
The brain has a tightly regulated environment that protects neurons and limits inflammation, designated "immune privilege." However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate-putamen (CP) and scored for an innate immune response and inhibition of virus spread...
January 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
Christiane Muth, Katharina Schröck, Charlotte Madore, Kristin Hartmann, Zain Fanek, Oleg Butovsky, Markus Glatzel, Susanne Krasemann
Prion diseases are fatal transmissible diseases, where conversion of the endogenous prion protein (PrP(C) ) into a misfolded isoform (PrP(Sc) ) leads to neurodegeneration. Microglia, the immune cells of the brain, are activated in neurodegenerative disorders including prion diseases, however their impact on prion disease pathophysiology is unclear with both beneficial PrP(Sc) -clearing and detrimental potentially neurotoxic effects. Moreover, monocytes entering the brain from the periphery during disease course might add to disease pathophysiology...
August 25, 2016: Brain Pathology
Jean-Christophe Delpech, Lan Wei, Jin Hao, Xiaoqing Yu, Charlotte Madore, Oleg Butovsky, Arie Kaffman
Children exposed to abuse or neglect show abnormal hippocampal development and similar findings have been reported in rodent models. Using brief daily separation (BDS), a mouse model of early life stress, we previously showed that exposure to BDS impairs hippocampal function in adulthood and perturbs synaptic maturation, synaptic pruning, axonal growth and myelination in the developing hippocampus. Given that microglia are involved in these developmental processes, we tested whether BDS impairs microglial activity in the hippocampus of 14 (during BDS) and 28-day old mice (one week after BDS)...
October 2016: Brain, Behavior, and Immunity
Kanchan Bisht, Kaushik P Sharma, Cynthia Lecours, Maria Gabriela Sánchez, Hassan El Hajj, Giampaolo Milior, Adrián Olmos-Alonso, Diego Gómez-Nicola, Giamal Luheshi, Luc Vallières, Igor Branchi, Laura Maggi, Cristina Limatola, Oleg Butovsky, Marie-Ève Tremblay
The past decade has witnessed a revolution in our understanding of microglia. These immune cells were shown to actively remodel neuronal circuits, leading to propose new pathogenic mechanisms. To study microglial implication in the loss of synapses, the best pathological correlate of cognitive decline across chronic stress, aging, and diseases, we recently conducted ultrastructural analyses. Our work uncovered the existence of a new microglial phenotype that is rarely present under steady state conditions, in hippocampus, cerebral cortex, amygdala, and hypothalamus, but becomes abundant during chronic stress, aging, fractalkine signaling deficiency (CX3 CR1 knockout mice), and Alzheimer's disease pathology (APP-PS1 mice)...
May 2016: Glia
Oleg Butovsky, Mark P Jedrychowski, Craig S Moore, Ron Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M Wu, Camille E Doykan, Zain Fanek, LiPing Liu, Zhuoxun Chen, Jeffrey D Rothstein, Richard M Ransohoff, Steven P Gygi, Jack P Antel, Howard L Weiner
No abstract text is available yet for this article.
December 2015: International Journal of Developmental Neuroscience
Oleg Butovsky, Mark P Jedrychowski, Ron Cialic, Gopal Murugaiyan, Pauline M Wu, Camille E Doykan, Zain Fanek, David J Greco, Olga Kiner, Robert J Lawson, Matthew P Frosch, Nathalie Pochet, Anna M Krichevsky, Steven P Gygi, James Berry, Merit E Cudkowicz, Howard L Weiner
No abstract text is available yet for this article.
December 2015: International Journal of Developmental Neuroscience
Hirohide Asai, Seiko Ikezu, Satoshi Tsunoda, Maria Medalla, Jennifer Luebke, Tarik Haydar, Benjamin Wolozin, Oleg Butovsky, Sebastian Kügler, Tsuneya Ikezu
Accumulation of pathological tau protein is a major hallmark of Alzheimer's disease. Tau protein spreads from the entorhinal cortex to the hippocampal region early in the disease. Microglia, the primary phagocytes in the brain, are positively correlated with tau pathology, but their involvement in tau propagation is unknown. We developed an adeno-associated virus-based model exhibiting rapid tau propagation from the entorhinal cortex to the dentate gyrus in 4 weeks. We found that depleting microglia dramatically suppressed the propagation of tau and reduced excitability in the dentate gyrus in this mouse model...
November 2015: Nature Neuroscience
Simon Verheijden, Lien Beckers, Andrea Casazza, Oleg Butovsky, Massimiliano Mazzone, Myriam Baes
The functional diversity and molecular adaptations of reactive microglia in the chronically inflamed central nervous system (CNS) are poorly understood. We previously showed that mice lacking multifunctional protein 2 (MFP2), a pivotal enzyme in peroxisomal β-oxidation, persistently accumulate reactive myeloid cells in the gray matter of the CNS. Here, we show that the increased numbers of myeloid cells solely derive from the proliferation of resident microglia and not from infiltrating monocytes. We defined the signature of Mfp2(-/-) microglia by gene expression profiling after acute isolation, which was validated by quantitative polymerase reaction (qPCR), immunohistochemical, and flow cytometric analysis...
September 2015: Glia
Craig S Moore, Ariel R Ase, Angham Kinsara, Vijayaraghava T S Rao, Mackenzie Michell-Robinson, Soo Yuen Leong, Oleg Butovsky, Samuel K Ludwin, Philippe Séguéla, Amit Bar-Or, Jack P Antel
OBJECTIVE: To investigate and measure the functional significance of altered P2Y12 expression in the context of human microglia activation. METHODS: We performed in vitro and in situ experiments to measure how P2Y12 expression can influence disease-relevant functional properties of classically activated (M1) and alternatively activated (M2) human microglia in the inflamed brain. RESULTS: We demonstrated that compared to resting and classically activated (M1) human microglia, P2Y12 expression is increased under alternatively activated (M2) conditions...
April 2015: Neurology® Neuroimmunology & Neuroinflammation
Taylor R Jay, Crystal M Miller, Paul J Cheng, Leah C Graham, Shane Bemiller, Margaret L Broihier, Guixiang Xu, Daniel Margevicius, J Colleen Karlo, Gregory L Sousa, Anne C Cotleur, Oleg Butovsky, Lynn Bekris, Susan M Staugaitis, James B Leverenz, Sanjay W Pimplikar, Gary E Landreth, Gareth R Howell, Richard M Ransohoff, Bruce T Lamb
Variants in triggering receptor expressed on myeloid cells 2 (TREM2) confer high risk for Alzheimer's disease (AD) and other neurodegenerative diseases. However, the cell types and mechanisms underlying TREM2's involvement in neurodegeneration remain to be established. Here, we report that TREM2 is up-regulated on myeloid cells surrounding amyloid deposits in AD mouse models and human AD tissue. TREM2 was detected on CD45(hi)Ly6C(+) myeloid cells, but not on P2RY12(+) parenchymal microglia. In AD mice deficient for TREM2, the CD45(hi)Ly6C(+) macrophages are virtually eliminated, resulting in reduced inflammation and ameliorated amyloid and tau pathologies...
March 9, 2015: Journal of Experimental Medicine
Oleg Butovsky, Mark P Jedrychowski, Ron Cialic, Susanne Krasemann, Gopal Murugaiyan, Zain Fanek, David J Greco, Pauline M Wu, Camille E Doykan, Olga Kiner, Robert J Lawson, Matthew P Frosch, Nathalie Pochet, Rachid El Fatimy, Anna M Krichevsky, Steven P Gygi, Hans Lassmann, James Berry, Merit E Cudkowicz, Howard L Weiner
OBJECTIVE: To investigate miR-155 in the SOD1 mouse model and human sporadic and familial amyotrophic lateral sclerosis (ALS). METHODS: NanoString microRNA, microglia and immune gene profiles, protein mass spectrometry, and RNA-seq analyses were measured in spinal cord microglia, splenic monocytes, and spinal cord tissue from SOD1 mice and in spinal cord tissue of familial and sporadic ALS. miR-155 was targeted by genetic ablation or by peripheral or centrally administered anti-miR-155 inhibitor in SOD1 mice...
January 2015: Annals of Neurology
Oleg Butovsky, Mark P Jedrychowski, Craig S Moore, Ron Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M Wu, Camille E Doykan, Zain Fanek, LiPing Liu, Zhuoxun Chen, Jeffrey D Rothstein, Richard M Ransohoff, Steven P Gygi, Jack P Antel, Howard L Weiner
No abstract text is available yet for this article.
August 26, 2014: Nature Neuroscience
Ryo Yamasaki, Haiyan Lu, Oleg Butovsky, Nobuhiko Ohno, Anna M Rietsch, Ron Cialic, Pauline M Wu, Camille E Doykan, Jessica Lin, Anne C Cotleur, Grahame Kidd, Musab M Zorlu, Nathan Sun, Weiwei Hu, LiPing Liu, Jar-Chi Lee, Sarah E Taylor, Lindsey Uehlein, Debra Dixon, Jinyu Gu, Crina M Floruta, Min Zhu, Israel F Charo, Howard L Weiner, Richard M Ransohoff
In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell-mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood...
July 28, 2014: Journal of Experimental Medicine
Oleg Butovsky, Mark P Jedrychowski, Craig S Moore, Ron Cialic, Amanda J Lanser, Galina Gabriely, Thomas Koeglsperger, Ben Dake, Pauline M Wu, Camille E Doykan, Zain Fanek, Liping Liu, Zhuoxun Chen, Jeffrey D Rothstein, Richard M Ransohoff, Steven P Gygi, Jack P Antel, Howard L Weiner
Microglia are myeloid cells of the CNS that participate both in normal CNS function and in disease. We investigated the molecular signature of microglia and identified 239 genes and 8 microRNAs that were uniquely or highly expressed in microglia versus myeloid and other immune cells. Of the 239 genes, 106 were enriched in microglia as compared with astrocytes, oligodendrocytes and neurons. This microglia signature was not observed in microglial lines or in monocytes recruited to the CNS, and was also observed in human microglia...
January 2014: Nature Neuroscience
Oleg Butovsky, Shafiuddin Siddiqui, Galina Gabriely, Amanda J Lanser, Ben Dake, Gopal Murugaiyan, Camille E Doykan, Pauline M Wu, Reddy R Gali, Lakshmanan K Iyer, Robert Lawson, James Berry, Anna M Krichevsky, Merit E Cudkowicz, Howard L Weiner
Amyotrophic lateral sclerosis (ALS) is a progressive disease associated with neuronal cell death that is thought to involve aberrant immune responses. Here we investigated the role of innate immunity in a mouse model of ALS. We found that inflammatory monocytes were activated and that their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We also found a decrease in resident microglia in the spinal cord with disease progression. Prior to disease onset, splenic Ly6Chi monocytes expressed a polarized macrophage phenotype (M1 signature), which included increased levels of chemokine receptor CCR2...
September 2012: Journal of Clinical Investigation
Ilan Vaknin, Gilad Kunis, Omer Miller, Oleg Butovsky, Shay Bukshpan, David R Beers, Jenny S Henkel, Eti Yoles, Stanley H Appel, Michal Schwartz
BACKGROUND: Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease...
2011: PloS One
Ruslan O Butovsky
Carabid beetles (Coleoptera, Carabidae) are one of the most studied soil groups in relation to heavy metal (HM) accumulation and use for bioindication of environmental pollution. Accumulation of Zn and Cu in carabid beetles was species-, sex- and trophic group-specific. No differences were found in HM contents between omnivorous and carnivorous species. The use of carabid beetles as indicators of HM accumulation appears to be rather limited.
2011: ZooKeys
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