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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 as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Liquid Phase-separation; Adult Brain; Stem-cells; Zebrafish; Progranulin; Model; Roles; Fus; Degeneration; Transition
ISSN (print) / ISBN 1097-6256
e-ISSN 1546-1726
Journal Nature Neuroscience
Quellenangaben Volume: 25, Issue: 12, Pages: 1608-1625 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
Lung Health and Immunity (LHI)
Institute of Computational Biology (ICB)
Grants 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