Merkler, Doron

[["dc.bibliographiccitation.firstpage","495"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","U135"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Nikic, Ivana"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Sorbara, Catherine"],["dc.contributor.author","Brinkoetter, Mary"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Bareyre, Florence Martine"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Bishop, Derron"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.date.accessioned","2018-11-07T08:57:32Z"],["dc.date.available","2018-11-07T08:57:32Z"],["dc.date.issued","2011"],["dc.description.abstract","In multiple sclerosis, a common inflammatory disease of the central nervous system, immune-mediated axon damage is responsible for permanent neurological deficits(1,2). How axon damage is initiated is not known. Here we use in vivo imaging to identify a previously undescribed variant of axon damage in a mouse model of multiple sclerosis. This process, termed 'focal axonal degeneration' (FAD), is characterized by sequential stages, beginning with focal swellings and progressing to axon fragmentation. Notably, most swollen axons persist unchanged for several days, and some recover spontaneously. Early stages of FAD can be observed in axons with intact myelin sheaths. Thus, contrary to the classical view(2-6), demyelination-a hallmark of multiple sclerosis-is not a prerequisite for axon damage. Instead, focal intra-axonal mitochondrial pathology is the earliest ultrastructural sign of damage, and it precedes changes in axon morphology. Molecular imaging and pharmacological experiments show that macrophage-derived reactive oxygen and nitrogen species (ROS and RNS) can trigger mitochondrial pathology and initiate FAD. Indeed, neutralization of ROS and RNS rescues axons that have already entered the degenerative process. Finally, axonal changes consistent with FAD can be detected in acute human multiple sclerosis lesions. In summary, our data suggest that inflammatory axon damage might be spontaneously reversible and thus a potential target for therapy."],["dc.identifier.doi","10.1038/nm.2324"],["dc.identifier.isi","000289245100041"],["dc.identifier.pmid","21441916"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23423"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1078-8956"],["dc.title","A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","eaav5519"],["dc.bibliographiccitation.issue","498"],["dc.bibliographiccitation.journal","Science Translational Medicine"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Steinbach, Karin"],["dc.contributor.author","Vincenti, Ilena"],["dc.contributor.author","Egervari, Kristof"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","van der Meer, Franziska"],["dc.contributor.author","Page, Nicolas"],["dc.contributor.author","Klimek, Bogna"],["dc.contributor.author","Rossitto-Borlat, Irène"],["dc.contributor.author","Di Liberto, Giovanni"],["dc.contributor.author","Muschaweckh, Andreas"],["dc.contributor.author","Wagner, Ingrid"],["dc.contributor.author","Hammad, Karim"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Korn, Thomas"],["dc.contributor.author","Hartley, Oliver"],["dc.contributor.author","Pinschewer, Daniel D."],["dc.contributor.author","Merkler, Doron"],["dc.date.accessioned","2020-12-10T18:36:47Z"],["dc.date.available","2020-12-10T18:36:47Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1126/scitranslmed.aav5519"],["dc.identifier.eissn","1946-6242"],["dc.identifier.issn","1946-6234"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/76737"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Brain-resident memory T cells generated early in life predispose to autoimmune disease in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","46"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","European Journal of Immunology"],["dc.bibliographiccitation.lastpage","57"],["dc.bibliographiccitation.volume","44"],["dc.contributor.author","Lalive, Patrice H."],["dc.contributor.author","Benkhoucha, Mahdia"],["dc.contributor.author","Ngoc Lan Tran, Ngoc Lan Tran"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Santiago-Raber, Marie-Laure"],["dc.date.accessioned","2018-11-07T09:46:42Z"],["dc.date.available","2018-11-07T09:46:42Z"],["dc.date.issued","2014"],["dc.identifier.isi","000330803400007"],["dc.identifier.pmid","24018482"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34941"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1521-4141"],["dc.relation.issn","0014-2980"],["dc.title","TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3(+) Treg cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2087"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Journal of Experimental Medicine"],["dc.bibliographiccitation.lastpage","2103"],["dc.bibliographiccitation.volume","210"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Bergthaler, Andreas"],["dc.contributor.author","Fernandez, Marylise"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Steinbach, Karin"],["dc.contributor.author","Vorm, Mariann"],["dc.contributor.author","Coras, Roland"],["dc.contributor.author","Bluemcke, Ingmar"],["dc.contributor.author","Bonilla, Weldy V."],["dc.contributor.author","Fleige, Anne"],["dc.contributor.author","Forman, Ruth"],["dc.contributor.author","Mueller, Werner"],["dc.contributor.author","Becher, Burkhard"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Pinschewer, Daniel D."],["dc.contributor.author","Merkler, Doron"],["dc.date.accessioned","2018-11-07T09:19:48Z"],["dc.date.available","2018-11-07T09:19:48Z"],["dc.date.issued","2013"],["dc.description.abstract","Neurons are postmitotic and thus irreplaceable cells of the central nervous system (CNS). Accordingly, CNS inflammation with resulting neuronal damage can have devastating consequences. We investigated molecular mediators and structural consequences of CD8(+) T lymphocyte (CTL) attack on neurons in vivo. In a viral encephalitis model in mice, disease depended on CTL-derived interferon-gamma (IFN-gamma) and neuronal IFN-gamma signaling. Downstream STAT1 phosphorylation and nuclear translocation in neurons were associated with dendrite and synapse loss (deafferentation). Analogous molecular and structural alterations were also found in human Rasmussen encephalitis, a CTL-mediated human autoimmune disorder of the CNS. Importantly, therapeutic intervention by IFN-gamma blocking antibody prevented neuronal deafferentation and clinical disease without reducing CTL responses or CNS infiltration. These findings identify neuronal IFN-gamma signaling as a novel target for neuroprotective interventions in CTL-mediated CNS disease."],["dc.identifier.doi","10.1084/jem.20122143"],["dc.identifier.isi","000324813000016"],["dc.identifier.pmid","23999498"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28728"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","0022-1007"],["dc.title","Neuroprotective intervention by interferon-gamma blockade prevents CD8(+) T cell-mediated dendrite and synapse loss"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","354"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cell Host & Microbe"],["dc.bibliographiccitation.lastpage","365.e5"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Remy, Melissa M."],["dc.contributor.author","Sahin, Mehmet"],["dc.contributor.author","Flatz, Lukas"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Xu, Lifen"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Fallet, Benedict"],["dc.contributor.author","Doras, Camille"],["dc.contributor.author","Rieger, Toni"],["dc.contributor.author","Bestmann, Lukas"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Kaufmann, Beat A."],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Pinschewer, Daniel D."],["dc.date.accessioned","2020-12-10T14:23:06Z"],["dc.date.available","2020-12-10T14:23:06Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1016/j.chom.2017.07.008"],["dc.identifier.issn","1931-3128"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71834"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","984"],["dc.bibliographiccitation.issue","6071"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","989"],["dc.bibliographiccitation.volume","335"],["dc.contributor.author","Bonilla, Weldy V."],["dc.contributor.author","Froehlich, Anja"],["dc.contributor.author","Senn, Karin"],["dc.contributor.author","Kallert, Sandra"],["dc.contributor.author","Fernandez, Marylise"],["dc.contributor.author","Johnson, Susan"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Hegazy, Ahmed N."],["dc.contributor.author","Schrick, Christina"],["dc.contributor.author","Fallon, Padraic G."],["dc.contributor.author","Klemenz, Roman"],["dc.contributor.author","Nakae, Susumu"],["dc.contributor.author","Adler, Heiko"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Loehning, Max"],["dc.contributor.author","Pinschewer, Daniel D."],["dc.date.accessioned","2018-11-07T09:13:18Z"],["dc.date.available","2018-11-07T09:13:18Z"],["dc.date.issued","2012"],["dc.description.abstract","Pathogen-associated molecular patterns decisively influence antiviral immune responses, whereas the contribution of endogenous signals of tissue damage, also known as damage-associated molecular patterns or alarmins, remains ill defined. We show that interleukin-33 (IL-33), an alarmin released from necrotic cells, is necessary for potent CD8(+) T cell (CTL) responses to replicating, prototypic RNA and DNA viruses in mice. IL-33 signaled through its receptor on activated CTLs, enhanced clonal expansion in a CTL-intrinsic fashion, determined plurifunctional effector cell differentiation, and was necessary for virus control. Moreover, recombinant IL-33 augmented vaccine-induced CTL responses. Radio-resistant cells of the splenic T cell zone produced IL-33, and efficient CTL responses required IL-33 from radio-resistant cells but not from hematopoietic cells. Thus, alarmin release by radio-resistant cells orchestrates protective antiviral CTL responses."],["dc.identifier.doi","10.1126/science.1215418"],["dc.identifier.isi","000300931800051"],["dc.identifier.pmid","22323740"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27144"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Advancement Science"],["dc.relation.issn","0036-8075"],["dc.title","The Alarmin Interleukin-33 Drives Protective Antiviral CD8(+) T Cell Responses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","355"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","367"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Jafari, Mehrnoosh"],["dc.contributor.author","Schumacher, Adrian-Minh"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Ullrich Gavilanes, Emily M."],["dc.contributor.author","Neziraj, Tradite"],["dc.contributor.author","Kocsis-Jutka, Virág"],["dc.contributor.author","Engels, Daniel"],["dc.contributor.author","Jürgens, Tanja"],["dc.contributor.author","Wagner, Ingrid"],["dc.contributor.author","Weidinger, Juan Daniel Flórez"],["dc.contributor.author","Schmidt, Stephanie S."],["dc.contributor.author","Beltrán, Eduardo"],["dc.contributor.author","Hagan, Nellwyn"],["dc.contributor.author","Woodworth, Lisa"],["dc.contributor.author","Ofengeim, Dimitry"],["dc.contributor.author","Gans, Joseph"],["dc.contributor.author","Wolf, Fred"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Portugues, Ruben"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.date.accessioned","2021-04-14T08:30:17Z"],["dc.date.available","2021-04-14T08:30:17Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1038/s41593-020-00780-7"],["dc.identifier.pmid","33495636"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83177"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/12"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/103"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B03: Checkpoints of recovery after primary astrocytic lesions in neuromyelitis optica and related animal models"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation","TRR 274 | C05: Checkpoints for circuit integration of nascent neurons in the injured brain"],["dc.relation","TRR 274 | Z01: Bioimaging Platform"],["dc.relation","TRR 274 | Z02: Genomics and Bioinformatics Platform"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | C02: Aktive Zonendesigns und -dynamiken, die auf das synaptische Arbeitsgedächtnis zugeschnitten sind"],["dc.relation.eissn","1546-1726"],["dc.relation.issn","1097-6256"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Portugues (Sensorimotor Control)"],["dc.relation.workinggroup","RG Wolf"],["dc.title","Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","640"],["dc.bibliographiccitation.journal","Science Translational Medicine"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Vincenti, Ilena"],["dc.contributor.author","Page, Nicolas"],["dc.contributor.author","Steinbach, Karin"],["dc.contributor.author","Yermanos, Alexander"],["dc.contributor.author","Lemeille, Sylvain"],["dc.contributor.author","Nunez, Nicolas"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Klimek, Bogna"],["dc.contributor.author","Di Liberto, Giovanni"],["dc.contributor.author","Egervari, Kristof"],["dc.contributor.author","Merkler, Doron"],["dc.date.accessioned","2022-05-02T08:02:31Z"],["dc.date.available","2022-05-02T08:02:31Z"],["dc.date.issued","2022"],["dc.description.abstract","In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (T RM ) represent a potentially important cellular player in this process. Here, we investigated whether resting CD8 + T RM persisting after cleared infection with attenuated lymphocytic choriomeningitis virus (LCMV) can initiate immune responses directed against cognate self-antigen in the CNS. We demonstrated that time-delayed conditional expression of the LCMV glycoprotein as neo-self-antigen by glia cells reactivated CD8 + T RM . Subsequently, CD8 + T RM expanded and initiated CNS inflammation and immunopathology in an organ-autonomous manner independently of circulating CD8 + T cells. However, in the absence of CD4 + T cells, TCF-1 + CD8 + T RM failed to expand and differentiate into terminal effectors. Similarly, in human demyelinating CNS autoimmune lesions, we found CD8 + T cells expressing TCF-1 that predominantly exhibited a T RM -like phenotype. Together, our study provides evidence for CD8 + T RM -driven CNS immunopathology and sheds light on why inflammatory processes may evade current immunomodulatory treatments in chronic autoimmune CNS conditions.\r\nT RM generated after resolved brain virus infection that cross-react with CNS-specific self-antigen orchestrate a compartmentalized autoimmune disease.\r\nA local contribution to CNS autoimmunity Aberrantly activated tissue-resident memory T cells (T RM ) have been shown to contribute to inflammatory conditions. Their role in the CNS remains unclear. Now, in two complementary studies, Vincenti et al. and Frieser et al. investigated the role of T RM in the CNS. Vincenti and colleagues reported that after viral brain infection, T RM triggered CNS inflammation, promoting autoimmune reactions in mice. Cells with T RM -like phenotype were also identified in brain tissue from patients with CNS autoimmune diseases. Frieser et al. used rodent models of CNS autoimmunity to show that pathogenic CD8 + T cells infiltrating the CNS adopted a T RM phenotype that contributes to the disease. The results suggest that targeting T RM can be effective in treating CNS autoimmune diseases."],["dc.identifier.doi","10.1126/scitranslmed.abl6058"],["dc.identifier.pmid","35417190"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107347"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/64"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/474"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1946-6242"],["dc.relation.issn","1946-6234"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.title","Tissue-resident memory CD8 + T cells cooperate with CD4 + T cells to drive compartmentalized immunopathology in the CNS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","227"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","244"],["dc.bibliographiccitation.volume","71"],["dc.contributor.author","Manrique-Hoyos, Natalia"],["dc.contributor.author","Juergens, Tanja"],["dc.contributor.author","Gronborg, Mads"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Schedensack, Mariann"],["dc.contributor.author","Kuhlmann, Tanja"],["dc.contributor.author","Schrick, Christina"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Merkler, Doron"],["dc.date.accessioned","2018-11-07T09:13:41Z"],["dc.date.available","2018-11-07T09:13:41Z"],["dc.date.issued","2012"],["dc.description.abstract","Objective: To investigate the impact of single or repeated episodes of reversible demyelination on long-term locomotor performance and neuroaxonal integrity, and to analyze the myelin proteome after remyelination and during aging. Methods: Long-term locomotor performance of previously cuprizone-treated animals was monitored using the motor skill sequence (MOSS). Quantitative analysis of myelin proteome and histopathological analysis of neuronal/ axonal integrity was performed after successful remyelination. Histopathological findings observed in experimental chronic remyelinated lesions were verified in chronic remyelinated lesions from multiple sclerosis (MS) patients. Results: Following cessation of cuprizone treatment, animals showed an initial recovery of locomotor performance. However, long after remyelination was completed (approximately 6 months after the last demyelinating episode), locomotor performance again declined in remyelinated animals as compared to age-matched controls. This functional decline was accompanied by brain atrophy and callosal axonal loss. Furthermore, the number of acutely damaged amyloid precursor protein-positive (APP_) axons was still significantly elevated in long-term remyelinated animals as compared to age-matched controls. Confocal analysis revealed that a substantial proportion of these APP_ spheroids were ensheathed by myelin, a finding that was confirmed in the chronic remyelinated lesions of MS patients. Moreover, quantitative analysis of myelin proteome revealed that remyelinated myelin displays alterations in composition that are in some aspects similar to the myelin of older animals. Interpretation: We propose that even after completed remyelination, axonal degeneration continues to progress at a low level, accumulating over time, and that once a threshold is passed axonal degeneration can become functionally apparent in the long-term. The presented model thus mimics some of the aspects of axonal degeneration in chronic progressive MS."],["dc.identifier.doi","10.1002/ana.22681"],["dc.identifier.isi","000300715300012"],["dc.identifier.pmid","22367995"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27232"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0364-5134"],["dc.title","Late motor decline after accomplished remyelination: Impact for progressive multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","39"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","46"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Juergens, Tanja"],["dc.contributor.author","Jafari, Mehrnoosh"],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Bahn, Erik"],["dc.contributor.author","Bruck, Wolfgang W."],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Merkler, Doron"],["dc.date.accessioned","2018-11-07T10:21:01Z"],["dc.date.available","2018-11-07T10:21:01Z"],["dc.date.issued","2016"],["dc.description.abstract","Grey matter pathology has emerged as an important contributor to long-term disability in multiple sclerosis. To better understand where and how neuronal damage in the grey matter is initiated, we used high resolution confocal microscopy of Golgi-Cox impregnated tissue sections and reconstructed single cortical projection neurons in autopsies from eight patients with long-standing relapsing-remitting or secondary progressive multiple sclerosis and eight control patients without neurological disease. Analysis of several hundred individual neurons located in the insular, frontotemporal and occipital lobe revealed a widespread and pronounced loss of dendritic spines in multiple sclerosis cortex that occurs independent of cortical demyelination and axon loss. The presence of a primary synaptic pathology in the normal-appearing cortex of multiple sclerosis patients challenges current disease concepts and has important implications for our understanding of disease progression."],["dc.identifier.doi","10.1093/brain/awv353"],["dc.identifier.isi","000370205000016"],["dc.identifier.pmid","26667278"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42004"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.title","Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]