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@ARTICLE{Breer:276776,
author = {Breßer, Mona and Siemens, Kevin D and Schneider, Linda and
Lunnebach, Jonah E and Leven, Patrick and Glowka, Tim R and
Oberländer, Kristin and De Domenico, Elena and Schultze,
Joachim L and Schmidt, Joachim and Kalff, Jörg C and
Schneider, Anja and Wehner, Sven and Schneider, Reiner},
title = {{M}acrophage-induced enteric neurodegeneration leads to
motility impairment during gut inflammation.},
journal = {EMBO molecular medicine},
volume = {17},
number = {2},
issn = {1757-4676},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2025-00315},
pages = {301 - 335},
year = {2025},
abstract = {Current studies pictured the enteric nervous system and
macrophages as modulators of neuroimmune processes in the
inflamed gut. Expanding this view, we investigated the
impact of enteric neuron-macrophage interactions on
postoperative trauma and subsequent motility disturbances,
i.e., postoperative ileus. In the early postsurgical phase,
we detected strong neuronal activation, followed by
transcriptional and translational signatures indicating
neuronal death and synaptic damage. Simultaneously, our
study revealed neurodegenerative profiles in
macrophage-specific transcriptomes after postoperative
trauma. Validating the role of resident and monocyte-derived
macrophages, we depleted macrophages by CSF-1R-antibodies
and used CCR2-/- mice, known for reduced monocyte
infiltration, in POI studies. Only CSF-1R-antibody-treated
animals showed decreased neuronal death and lessened
synaptic decay, emphasizing the significance of resident
macrophages. In human gut samples taken early and late
during abdominal surgery, we substantiated the mouse model
data and found reactive and apoptotic neurons and
dysregulation in synaptic genes, indicating a species'
overarching mechanism. Our study demonstrates that surgical
trauma activates enteric neurons and induces
neurodegeneration, mediated by resident macrophages,
introducing neuroprotection as an option for faster recovery
after surgery.},
keywords = {Animals / Macrophages: metabolism / Humans / Mice /
Gastrointestinal Motility / Enteric Nervous System:
pathology / Enteric Nervous System: physiopathology /
Disease Models, Animal / Inflammation: pathology / Neurons:
pathology / Neurons: metabolism / Mice, Inbred C57BL / Male
/ Mice, Knockout / Enteric Neurons (Other) / Macrophages
(Other) / Neuroimmune Interaction (Other) / Postoperative
Ileus (Other) / Synaptic Damage (Other)},
cin = {AG Schneider / AG Schultze / PRECISE},
ddc = {610},
cid = {I:(DE-2719)1011305 / I:(DE-2719)1013038 /
I:(DE-2719)1013031},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 354 -
Disease Prevention and Healthy Aging (POF4-354) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-354 /
G:(DE-HGF)POF4-352},
experiment = {EXP:(DE-2719)PRECISE-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39762650},
pmc = {pmc:PMC11822118},
doi = {10.1038/s44321-024-00189-w},
url = {https://pub.dzne.de/record/276776},
}