TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury
Zambusi A, Novoselc KT, Hutten S, Kalpazidou S, Koupourtidou C, Schieweck R, Aschenbroich S, Silva L, Yazgili AS, Van Bebber F, Schmid B, Moeller G, Tritscher C, Stigloher C, Delbridge C, Sirko S, Gunes ZI, Liebscher S, Schlegel J, Aliee H, Theis F, Meiners S, Kiebler M, Dormann D, Ninkovic J (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 25
Pages Range: 1608-1625
Journal Issue: 12
DOI: 10.1038/s41593-022-01199-y
Abstract
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.
Involved external institutions
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Germany (DE)
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
How to cite
APA:
Zambusi, A., Novoselc, K.T., Hutten, S., Kalpazidou, S., Koupourtidou, C., Schieweck, R.,... Ninkovic, J. (2022). TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury. Nature Neuroscience, 25(12), 1608-1625. https://dx.doi.org/10.1038/s41593-022-01199-y
MLA:
Zambusi, Alessandro, et al. "TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury." Nature Neuroscience 25.12 (2022): 1608-1625.
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