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Zambusi, A. ; Novoselc, K.T. ; Hutten, S.* ; Kalpazidou, S.* ; Koupourtidou, C.* ; Schieweck, R.* ; Aschenbroich, S.* ; Silva, L.* ; Yazgili, A.S. ; van Bebber, F.* ; Schmid, B.* ; Möller, G.* ; Tritscher, C.* ; Stigloher, C.* ; Delbridge, C.* ; Sirko, S. ; Günes, Z.I.* ; Liebscher, S.* ; Schlegel, J.* ; Aliee, H. ; Theis, F.J. ; Meiners, S. ; Kiebler, M.* ; Dormann, D.* ; Ninkovic, J.

TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury.

Nat. Neurosci. 25, 1608-1625 (2022)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Decreasing the activation of pathology-activated microglia is crucial to prevent chronic inflammation and tissue scarring. In this study, we used a stab wound injury model in zebrafish and identified an injury-induced microglial state characterized by the accumulation of lipid droplets and TAR DNA-binding protein of 43 kDa (TDP-43)+ condensates. Granulin-mediated clearance of both lipid droplets and TDP-43+ condensates was necessary and sufficient to promote the return of microglia back to the basal state and achieve scarless regeneration. Moreover, in postmortem cortical brain tissues from patients with traumatic brain injury, the extent of microglial activation correlated with the accumulation of lipid droplets and TDP-43+ condensates. Together, our results reveal a mechanism required for restoring microglia to a nonactivated state after injury, which has potential for new therapeutic applications in humans.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Liquid Phase-separation; Adult Brain; Stem-cells; Zebrafish; Progranulin; Model; Roles; Fus; Degeneration; Transition
ISSN (print) / ISBN 1097-6256
e-ISSN 1546-1726
Zeitschrift Nature Neuroscience
Quellenangaben Band: 25, Heft: 12, Seiten: 1608-1625 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
Lung Health and Immunity (LHI)
Institute of Computational Biology (ICB)
Förderungen Ludwig-Maximilians-Universitat Munchen
Gutenberg Forschungskolleg
Fritz Thyssen Stiftung
Deutsche Forschungsgemeinschaft
Munich Cluster for Systems Neurology
JGU Mainz
Graduate School for Systemic Neurosciences GSN-LMU
Forschungsinitiative des Landes Rheinland-Pfalz
Ampro Helmholtz Alliance