Hanisch, Uwe-Karsten

[["dc.bibliographiccitation.firstpage","461"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Physiological Reviews"],["dc.bibliographiccitation.lastpage","553"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Noda, Mami"],["dc.contributor.author","Verkhratsky, Alexei"],["dc.date.accessioned","2018-11-07T08:57:18Z"],["dc.date.available","2018-11-07T08:57:18Z"],["dc.date.issued","2011"],["dc.description.abstract","Kettenmann H, Hanisch U-K, Noda M, Verkhratsky A. Physiology of Microglia. Physiol Rev 91: 461-553, 2011; doi:10.1152/physrev.00011.2010.-Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed \"resting microglia.\" Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the \"activated microglial cell.\" This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments."],["dc.identifier.doi","10.1152/physrev.00011.2010"],["dc.identifier.isi","000290017800003"],["dc.identifier.pmid","21527731"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23361"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","1522-1210"],["dc.relation.issn","0031-9333"],["dc.title","Physiology of Microglia"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1083"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1099"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","John, Michael"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Borisch, Angela"],["dc.contributor.author","Boutin, Philippe"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Bremes, Vanessa"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Waetzig, Vicky"],["dc.contributor.author","Herdegen, Thomas"],["dc.contributor.author","Teismann, Peter"],["dc.contributor.author","Greig, Iain"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Rotshenker, Shlomo"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T09:56:53Z"],["dc.date.available","2018-11-07T09:56:53Z"],["dc.date.issued","2015"],["dc.description.abstract","The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK inhibition cannot account for the entire activity spectrum. Effects on TLR-induced proinflammatory cytokine expression in microglia involve AG126 hydrolysis and conversion of its dinitrile side chain to malononitrile (MN). Notably, while liberated MN can subsequently mediate critical AG126 features, full protection in EAE still requires delivery of intact AG126. Its anti-inflammatory potential and especially interference with TLR signaling thus rely on a dual mechanism encompassing BTK and a novel MN-sensitive target. Both principles bear great potential for the therapeutic management of disturbed innate and adaptive immune functions. GLIA 2015;63:1083-1099"],["dc.identifier.doi","10.1002/glia.22803"],["dc.identifier.isi","000353244400011"],["dc.identifier.pmid","25731696"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37056"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Tyrphostin AG126 Exerts Neuroprotection in CNS Inflammation by a Dual Mechanism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1930"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1943"],["dc.bibliographiccitation.volume","60"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Seifert, Stefanie"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Parsa, Roham"],["dc.contributor.author","Harris, Robert A."],["dc.contributor.author","Boddeke, Hendrikus W. G. M."],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Wessels, Johannes Theodor"],["dc.contributor.author","Juergens, Tanja"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Schnaars, Mareike"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T09:03:06Z"],["dc.date.available","2018-11-07T09:03:06Z"],["dc.date.issued","2012"],["dc.description.abstract","The sentinel and immune functions of microglia require rapid and appropriate reactions to infection and damage. Their Toll-like receptors (TLRs) sense both as threats. However, whether activated microglia mount uniform responses or whether subsets conduct selective tasks is unknown. We demonstrate that murine microglia reorganize their responses to TLR activations postnatally and that this process comes with a maturation of TLR4-organized functions. Although induction of MHCI for antigen presentation remains as a pan-populational feature, synthesis of TNFa becomes restricted to a subset, even within adult central nervous system regions. Response heterogeneity is evident ex vivo, in situ, and in vivo, but is not limited to TNFa production or to TLR-triggered functions. Also, clearance activities for myelin under physiological and pathophysiological conditions, IFN >> factors reveal dissimilar microglial contributions. Notably, response heterogeneity is also confirmed in human brain tissue. Our findings suggest that microglia divide by constitutive and inducible capacities. Privileged production of inflammatory mediators assigns a master control to subsets. Sequestration of clearance of endogenous material versus antigen presentation in exclusive compartments can separate potentially interfering functions. Finally, subsets rather than a uniform population of microglia may assemble the reactive phenotypes in responses during infection, injury, and rebuilding, warranting consideration in experimental manipulation and therapeutic strategies. (c) 2012 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/glia.22409"],["dc.identifier.isi","000310262600010"],["dc.identifier.pmid","22911652"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24833"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.title","Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cytokine"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Rossum van, Denise"],["dc.contributor.author","Weinstein, Jonathan R."],["dc.contributor.author","Dihazi, Hassan"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Moeller, Thomas"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T11:11:15Z"],["dc.date.available","2018-11-07T11:11:15Z"],["dc.date.issued","2008"],["dc.format.extent","315"],["dc.identifier.doi","10.1016/j.cyto.2008.07.386"],["dc.identifier.isi","000260212900351"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53386"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Ltd Elsevier Science Ltd"],["dc.publisher.place","London"],["dc.relation.conference","7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research"],["dc.relation.eventlocation","Montreal, CANADA"],["dc.relation.issn","1043-4666"],["dc.title","Toll-like receptor 4/MyD88 pathway mediates microglial proinflammatory cytokine responses to thrombin-associated coagulation protein complexes"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1457"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Neuro-Oncology"],["dc.bibliographiccitation.lastpage","1468"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Vinnakota, Katyayni"],["dc.contributor.author","Hu, Feng"],["dc.contributor.author","Ku, Min-Chi"],["dc.contributor.author","Georgieva, Petya B."],["dc.contributor.author","Szulzewsky, Frank"],["dc.contributor.author","Pohlmann, Andreas"],["dc.contributor.author","Waiczies, Sonia"],["dc.contributor.author","Waiczies, Helmar"],["dc.contributor.author","Niendorf, Thoralf"],["dc.contributor.author","Lehnardt, Seija"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Synowitz, Michael"],["dc.contributor.author","Markovic, Darko"],["dc.contributor.author","Wolf, Susanne A."],["dc.contributor.author","Glass, Rainer"],["dc.contributor.author","Kettenmann, Helmut"],["dc.date.accessioned","2018-11-07T09:18:01Z"],["dc.date.available","2018-11-07T09:18:01Z"],["dc.date.issued","2013"],["dc.description.abstract","Glioblastomas are the most aggressive primary brain tumors in humans. Microglia/brain macrophage accumulation in and around the tumor correlates with malignancy and poor clinical prognosis of these tumors. We have previously shown that microglia promote glioma expansion through upregulation of membrane type 1 matrix metalloprotease (MT1-MMP). This upregulation depends on signaling via the Toll-like receptor (TLR) adaptor molecule myeloid differentiation primary response gene 88 (MyD88). Using in vitro, ex vivo, and in vivo techniques, we identified TLR2 as the main TLR controlling microglial MT1-MMP expression and promoting microglia-assisted glioma expansion. The implantation of mouse GL261 glioma cells into TLR2 knockout mice resulted in significantly smaller tumors, reduced MT1-MMP expression, and enhanced survival rates compared with wild-type control mice. Tumor expansion studied in organotypic brain slices depended on both parenchymal TLR2 expression and the presence of microglia. Glioma-derived soluble factors and synthetic TLR2 specific ligands induced MT1-MMP expression in microglia from wild-type mice, but no such change in MT1-MMP gene expression was observed in microglia from TLR2 knockout mice. We also found evidence that TLR1 and TLR6 cofunction with TLR2 as heterodimers in regulating MT1-MMP expression in vitro. Our results thus show that activation of TLR2 along with TLRs 1 and/or 6 converts microglia into a glioma supportive phenotype."],["dc.identifier.doi","10.1093/neuonc/not115"],["dc.identifier.isi","000326747900004"],["dc.identifier.pmid","24014382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28315"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press Inc"],["dc.relation.issn","1523-5866"],["dc.relation.issn","1522-8517"],["dc.title","Toll-like receptor 2 mediates microglia/brain macrophage MT1-MMP expression and glioma expansion"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1387"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","1394"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Kettenmann, Helmut"],["dc.date.accessioned","2018-11-07T10:57:18Z"],["dc.date.available","2018-11-07T10:57:18Z"],["dc.date.issued","2007"],["dc.description.abstract","Microglial cells constitute the resident macrophage population of the CNS. Recent in vivo studies have shown that microglia carry out active tissue scanning, which challenges the traditional notion of 'resting' microglia in the normal brain. Transformation of microglia to reactive states in response to pathology has been known for decades as microglial activation, but seems to be more diverse and dynamic than ever anticipated-in both transcriptional and nontranscriptional features and functional consequences. This may help to explain why engagement of microglia can be either neuroprotective or neurotoxic, resulting in containment or aggravation of disease progression. Moreover, little is known about the heterogeneity of microglial responses in different pathologic contexts that results from regional adaptations or from the progression of a disease. In this review, we focus on several key observations that illustrate the multi-faceted activities of microglia in the normal and pathologic brain."],["dc.identifier.doi","10.1038/nn1997"],["dc.identifier.isi","000250508400013"],["dc.identifier.pmid","17965659"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50208"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1097-6256"],["dc.title","Microglia: active sensor and versatile effector cells in the normal and pathologic brain"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Hu, Feng"],["dc.contributor.author","Vinnakota, Katyayni"],["dc.contributor.author","Ku, M.-C."],["dc.contributor.author","Georgieva, Petya B."],["dc.contributor.author","Szulzewsky, Frank"],["dc.contributor.author","Lehnardt, Seija"],["dc.contributor.author","Hanisch, U.-K."],["dc.contributor.author","Synowitz, Michael"],["dc.contributor.author","Markovic, Darko"],["dc.contributor.author","Glass, Rainer"],["dc.contributor.author","Wolf, S. A."],["dc.contributor.author","Kettenmann, Helmut"],["dc.date.accessioned","2018-11-07T09:23:22Z"],["dc.date.available","2018-11-07T09:23:22Z"],["dc.date.issued","2013"],["dc.format.extent","S213"],["dc.identifier.isi","000320408400691"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29561"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","11th European Meeting on Glial Cell Function in Health and Disease"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0894-1491"],["dc.title","TOLL-LIKE-RECEPTOR 2 MEDIATES MICROGLIA/BRAIN MACROPHAGE MT1-MMP EXPRESSION AND GLIOMA EXPANSION"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","205"],["dc.bibliographiccitation.journal","Brain Behavior and Immunity"],["dc.bibliographiccitation.lastpage","221"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Schaafsma, W."],["dc.contributor.author","Zhang, X."],["dc.contributor.author","van Zomeren, K. C."],["dc.contributor.author","Jacobs, S."],["dc.contributor.author","Georgieva, Petya B."],["dc.contributor.author","Wolf, S. A."],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Hanisch, U.-K."],["dc.contributor.author","Meerlo, Peter"],["dc.contributor.author","van den Elsen, Peter J."],["dc.contributor.author","Brouwer, Nieske"],["dc.contributor.author","Boddeke, Hendrikus W. G. M."],["dc.contributor.author","Eggen, Bart J. L."],["dc.date.accessioned","2018-11-07T09:53:59Z"],["dc.date.available","2018-11-07T09:53:59Z"],["dc.date.issued","2015"],["dc.description.abstract","Microglia, the innate immune cells of the central nervous system (CNS), react to endotoxins like bacterial lipopolysaccharides (LPS) with a pronounced inflammatory response. To avoid excess damage to the CNS, the microglia inflammatory response needs to be tightly regulated. Here we report that a single LPS challenge results in a prolonged blunted pro-inflammatory response to a subsequent LPS stimulation, both in primary microglia cultures (100 ng/ml) and in vivo after intraperitoneal (0.25 and 1 mg/kg) or intracere-broventricular (5 mu g) LPS administration. Chromatin immunoprecipitation (ChIP) experiments with primary microglia and microglia acutely isolated from mice showed that LPS preconditioning was accompanied by a reduction in active histone modifications AcH3 and H3K4me3 in the promoters of the IL-10 and TNF-alpha genes. Furthermore, LPS preconditioning resulted in an increase in the amount of repressive histone modification H3K9me2 in the IL-1 beta promoter. ChIP and knock-down experiments showed that NF-kappa B subunit RelB was bound to the IL-1 beta promoter in preconditioned microglia and that RelB is required for the attenuated LPS response. In addition to a suppressed pro-inflammatory response, preconditioned primary microglia displayed enhanced phagocytic activity, increased outward potassium currents and nitric oxide production in response to a second LPS challenge. In vivo, a single i.p. LPS injection resulted in reduced performance in a spatial learning task 4 weeks later, indicating that a single inflammatory episode affected memory formation in these mice. Summarizing, we show that LPS-preconditioned microglia acquire an epigenetically regulated, immune-suppressed phenotype, possibly to prevent excessive damage to the central nervous system in case of recurrent (peripheral) inflammation. (C) 2015 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.bbi.2015.03.013"],["dc.identifier.isi","000358460700023"],["dc.identifier.pmid","25843371"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36442"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1090-2139"],["dc.relation.issn","0889-1591"],["dc.title","Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","654"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","665"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Hoffmann, Anja"],["dc.contributor.author","Grimm, Christian"],["dc.contributor.author","Kraft, Robert"],["dc.contributor.author","Goldbaum, Olaf"],["dc.contributor.author","Wrede, Arne"],["dc.contributor.author","Nolte, Christiane"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Richter-Landsberg, Christiane"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Harteneck, Christian"],["dc.date.accessioned","2018-11-07T08:40:55Z"],["dc.date.available","2018-11-07T08:40:55Z"],["dc.date.issued","2010"],["dc.description.abstract","P>Oligodendrocytes are the myelin-forming cells of the CNS and guarantee proper nerve conduction. Sphingosine, one major component of myelin, has recently been identified to activate TRPM3, a member of the melastatin-related subfamily of transient receptor potential (TRP) channels. TRPM3 has been demonstrated to be expressed in brain with unknown cellular distribution. Here, we show for the first time that TRPM3 is expressed in oligodendrocytes in vitro and in vivo. TRPM3 is present during oligodendrocyte differentiation. Immunohistochemistry of adult rat brain slices revealed staining of white matter areas, which co-localized with oligodendrocyte markers. Analysis of the developmental distribution revealed that, prior to myelination, TRPM3 channels are localized on neurons. On oligodendrocytes they are found after the onset of myelination. RT-PCR studies showed that the transcription of TRPM3 splice variants is also developmentally regulated in vitro. Ca2+ imaging approaches revealed the presence of a sphingosine-induced Ca2+ entry mechanism in oligodendrocytes - with a pharmacological profile similar to the profile published for heterologously expressed TRPM3. These findings indicate that TRPM3 participates as a Ca2+-permeable and sphingosine-activated channel in oligodendrocyte differentiation and CNS myelination."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft; Sonnenfeld Stiftung"],["dc.identifier.doi","10.1111/j.1471-4159.2010.06644.x"],["dc.identifier.isi","000279541900003"],["dc.identifier.pmid","20163522"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19351"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0022-3042"],["dc.title","TRPM3 is expressed in sphingosine-responsive myelinating oligodendrocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1162"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1175"],["dc.bibliographiccitation.volume","56"],["dc.contributor.author","Hoffmann, Anja"],["dc.contributor.author","Hofmann, Fred"],["dc.contributor.author","Just, Ingo"],["dc.contributor.author","Lehnardt, Seija"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Ahnert-Hilger, Gudrun"],["dc.contributor.author","Hoeltje, Markus"],["dc.date.accessioned","2018-11-07T11:12:07Z"],["dc.date.available","2018-11-07T11:12:07Z"],["dc.date.issued","2008"],["dc.description.abstract","Successful regeneration in the central nervous system crucially depends on the adequate environment. Microglia as brain immune-competent cells importantly contribute to this task by producing pro- and anti-inflammatory media_ tors. Any environmental change transforms these cells towards an activated phenotype, leading to major morphological, transcriptional and functional alterations. Rho GTPases affect multiple cellular properties, including the cytoskeleton, and C3 proteins are widely used to study their involvement. Especially C3bot from Clostridium botulinurn has been considered to promote neuronal regeneration by changing Rho activity. Yet C3bot may exert cellular influences through alternative mechanisms. To determine the role of Rho-dependent pathways in microglia we investigated the influence of C3bot on functional properties of cultivated primary mouse microglial cells. Nanomolar concentrations of C3bot transformed microglia towards an activated phenotype and triggered the release of nitric oxide and several proinflammatory cyto- and chemokines. These inductions were not mediated by the ROCK-kinase pathway, since its selective inhibitors Y27632 and H1152 had no effect. C3-induced and Rho-mediated NO release was instead found to be under the control of NFKB, as revealed by treatment with the NFKB inhibitor PDTC. Thus, C3bot induces a proinflammatory response in microglia resembling the classical proinflammatory phenotype elicited by bacterial LPS. The findings are relevant for the use of C3bot in regenerative approaches. (c) 2008 Wiley-Liss, Inc."],["dc.identifier.doi","10.1002/glia.20687"],["dc.identifier.isi","000257903900002"],["dc.identifier.pmid","18442097"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53590"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.title","Inhibition of rho-dependent pathways by Clostridium botulinum C3 protein induces a proinflammatory profile in microglia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]