Publications

What is a Publication?
36 Publications visible to you, out of a total of 36
Brain injury environment critically influences the connectivity of transplanted neurons

Abstract (Expand)

Cell transplantation is a promising approach for the reconstruction of neuronal circuits after brain damage. Transplanted neurons integrate with remarkable specificity into circuitries of the mouse … cerebral cortex affected by neuronal ablation. However, it remains unclear how neurons perform in a local environment undergoing reactive gliosis, inflammation, macrophage infiltration, and scar formation, as in traumatic brain injury (TBI). To elucidate this, we transplanted cells from the embryonic mouse cerebral cortex into TBI-injured, inflamed-only, or intact cortex of adult mice. Brain-wide quantitative monosynaptic rabies virus (RABV) tracing unraveled graft inputs from correct regions across the brain in all conditions, with pronounced quantitative differences: scarce in intact and inflamed brain versus exuberant after TBI. In the latter, the initial overshoot is followed by pruning, with only a few input neurons persisting at 3 months. Proteomic profiling identifies candidate molecules for regulation of the synaptic yield, a pivotal parameter to tailor for functional restoration of neuronal circuits.

Authors: Sofia Grade, Judith Thomas, Yvette Zarb, Manja Thorwirth, Karl-Klaus Conzelmann, Stefanie M. Hauck, Magdalena Götz

Date Published: 10th Jun 2022

Publication Type: Journal Article

The lung microbiome regulates brain autoimmunity.

Abstract (Expand)

Lung infections and smoking are risk factors for multiple sclerosis, a T-cell-mediated autoimmune disease of the central nervous system(1). In addition, the lung serves as a niche for the disease-inducing … T cells for long-term survival and for maturation into migration-competent effector T cells(2). Why the lung tissue in particular has such an important role in an autoimmune disease of the brain is not yet known. Here we detected a tight interconnection between the lung microbiota and the immune reactivity of the brain. A dysregulation in the lung microbiome significantly influenced the susceptibility of rats to developing autoimmune disease of the central nervous system. Shifting the microbiota towards lipopolysaccharide-enriched phyla by local treatment with neomycin induced a type-I-interferon-primed state in brain-resident microglial cells. Their responsiveness towards autoimmune-dominated stimulation by type II interferons was impaired, which led to decreased proinflammatory response, immune cell recruitment and clinical signs. Suppressing lipopolysaccharide-producing lung phyla with polymyxin B led to disease aggravation, whereas addition of lipopolysaccharide-enriched phyla or lipopolysaccharide recapitulated the neomycin effect. Our data demonstrate the existence of a lung-brain axis in which the pulmonary microbiome regulates the immune reactivity of the central nervous tissue and thereby influences its susceptibility to autoimmune disease development.

Authors: L. Hosang, R. C. Canals, F. J. van der Flier, J. Hollensteiner, R. Daniel, A. Flugel, F. Odoardi

Date Published: 25th Feb 2022

Publication Type: Journal Article

Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitment to the Injury Site in Adult Zebrafish Brain

Abstract (Expand)

The oligodendrocyte progenitors (OPCs) are at the front of the glial reaction to the traumatic brain injury. However, regulatory pathways steering the OPC reaction as well as the role of reactive OPCs … remain largely unknown. Here, we compared a long-lasting, exacerbated reaction of OPCs to the adult zebrafish brain injury with a timely restricted OPC activation to identify the specific molecular mechanisms regulating OPC reactivity and their contribution to regeneration. We demonstrated that the influx of the cerebrospinal fluid into the brain parenchyma after injury simultaneously activates the toll-like receptor 2 (Tlr2) and the chemokine receptor 3 (Cxcr3) innate immunity pathways, leading to increased OPC proliferation and thereby exacerbated glial reactivity. These pathways were critical for long-lasting OPC accumulation even after the ablation of microglia and infiltrating monocytes. Importantly, interference with the Tlr1/2 and Cxcr3 pathways after injury alleviated reactive gliosis, increased new neuron recruitment, and improved tissue restoration.

Authors: Rosario Sanchez-Gonzalez, Christina Koupourtidou, Tjasa Lepko, Alessandro Zambusi, Klara Tereza Novoselc, Tamara Durovic, Sven Aschenbroich, Veronika Schwarz, Christopher T. Breunig, Hans Straka, Hagen B. Huttner, Martin Irmler, Johannes Beckers, Wolfgang Wurst, Andreas Zwergal, Tamas Schauer, Tobias Straub, Tim Czopka, Dietrich Trümbach, Magdalena Götz, Stefan H. Stricker, Jovica Ninkovic

Date Published: 2nd Feb 2022

Publication Type: Journal Article

Proteomic and lipidomic profiling of demyelinating lesions identifies fatty acids as modulators in lesion recovery

Abstract

Not specified

Authors: Horst Penkert, Alix Bertrand, Vini Tiwari, Stephan Breimann, Stephan A. Müller, Paul M. Jordan, Mathias J. Gerl, Christian Klose, Ludovico Cantuti-Castelvetri, Mar Bosch-Queralt, Ilya Levental, Stefan F. Lichtenthaler, Oliver Werz, Mikael Simons

Date Published: 1st Oct 2021

Publication Type: Journal Article

Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the proneural factors Ascl1 and Neurogenin2

Abstract

Not specified

Authors: J. Kempf, K. Knelles, B.A. Hersbach, D. Petrik, T. Riedemann, V. Bednarova, A. Janjic, T. Simon-Ebert, W. Enard, P. Smialowski, M. Götz, G. Masserdotti

Date Published: 1st Jul 2021

Publication Type: Journal Article

Skin and gut imprinted helper T cell subsets exhibit distinct functional phenotypes in central nervous system autoimmunity

Abstract

Not specified

Authors: Michael Hiltensperger, Eduardo Beltrán, Ravi Kant, Sofia Tyystjärvi, Gildas Lepennetier, Helena Domínguez Moreno, Isabel J. Bauer, Simon Grassmann, Sebastian Jarosch, Kilian Schober, Veit R. Buchholz, Selin Kenet, Christiane Gasperi, Rupert Öllinger, Roland Rad, Andreas Muschaweckh, Christopher Sie, Lilian Aly, Benjamin Knier, Garima Garg, Ali M. Afzali, Lisa Ann Gerdes, Tania Kümpfel, Sören Franzenburg, Naoto Kawakami, Bernhard Hemmer, Dirk H. Busch, Thomas Misgeld, Klaus Dornmair, Thomas Korn

Date Published: 7th Jun 2021

Publication Type: Journal Article

Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation

Abstract

Not specified

Authors: Mehrnoosh Jafari, Adrian-Minh Schumacher, Nicolas Snaidero, Emily M. Ullrich Gavilanes, Tradite Neziraj, Virág Kocsis-Jutka, Daniel Engels, Tanja Jürgens, Ingrid Wagner, Juan Daniel Flórez Weidinger, Stephanie S. Schmidt, Eduardo Beltrán, Nellwyn Hagan, Lisa Woodworth, Dimitry Ofengeim, Joseph Gans, Fred Wolf, Mario Kreutzfeldt, Ruben Portugues, Doron Merkler, Thomas Misgeld, Martin Kerschensteiner

Date Published: 25th Jan 2021

Publication Type: Journal Article

Powered by
 (v.1.17.4)
About FAIRDOM | Funding and Programmes | Credits
Copyright © 2008 - 2026 The University of Manchester and HITS gGmbH