Publications

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35 Publications visible to you, out of a total of 35
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

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

Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis

Abstract (Expand)

Remyelination requires innate immune system function, but how exactly microglia and macrophages clear myelin debris after injury and tailor a specific regenerative response is unclear. Here, we asked … whether pro-inflammatory microglial/macrophage activation is required for this process. We established a novel toxin-based spinal cord model of de- and remyelination in zebrafish and showed that pro-inflammatory NF-κB–dependent activation in phagocytes occurs rapidly after myelin injury. We found that the pro-inflammatory response depends on myeloid differentiation primary response 88 (MyD88). MyD88-deficient mice and zebrafish were not only impaired in the degradation of myelin debris, but also in initiating the generation of new oligodendrocytes for myelin repair. We identified reduced generation of TNF-α in lesions of MyD88-deficient animals, a pro-inflammatory molecule that was able to induce the generation of new premyelinating oligodendrocytes. Our study shows that pro-inflammatory phagocytic signaling is required for myelin debris degradation, for inflammation resolution, and for initiating the generation of new oligodendrocytes.

Authors: Maria Inês Cunha, Minhui Su, Ludovico Cantuti-Castelvetri, Stephan A. Müller, Martina Schifferer, Minou Djannatian, Ioannis Alexopoulos, Franziska van der Meer, Anne Winkler, Tjakko J. van Ham, Bettina Schmid, Stefan F. Lichtenthaler, Christine Stadelmann, Mikael Simons

Date Published: 20th Feb 2020

Publication Type: Journal Article

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