TY  - JOUR
AU  - Zambusi, Alessandro
AU  - Novoselc, Klara Tereza
AU  - Hutten, Saskia
AU  - Kalpazidou, Sofia
AU  - Koupourtidou, Christina
AU  - Schieweck, Rico
AU  - Aschenbroich, Sven
AU  - Silva, Lara
AU  - Yazgili, Ayse Seda
AU  - van Bebber, Frauke
AU  - Schmid, Bettina
AU  - Möller, Gabriel
AU  - Tritscher, Clara
AU  - Stigloher, Christian
AU  - Delbridge, Claire
AU  - Sirko, Swetlana
AU  - Günes, Zeynep Irem
AU  - Liebscher, Sabine
AU  - Schlegel, Jürgen
AU  - Aliee, Hananeh
AU  - Theis, Fabian
AU  - Meiners, Silke
AU  - Kiebler, Michael
AU  - Dormann, Dorothee
AU  - Ninkovic, Jovica
TI  - TDP-43 condensates and lipid droplets regulate the reactivity of microglia and regeneration after traumatic brain injury.
JO  - Nature neuroscience
VL  - 25
IS  - 12
SN  - 1097-6256
CY  - New York, NY
PB  - Nature America
M1  - DZNE-2022-01747
SP  - 1608 - 1625
PY  - 2022
AB  - 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.
KW  - Humans
KW  - Animals
KW  - Microglia
KW  - Lipid Droplets
KW  - Zebrafish
KW  - Brain Injuries, Traumatic
KW  - DNA-Binding Proteins
KW  - Regeneration
KW  - DNA-Binding Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36424432
DO  - DOI:10.1038/s41593-022-01199-y
UR  - https://pub.dzne.de/record/165614
ER  -