TY  - JOUR
AU  - Breßer, Mona
AU  - Siemens, Kevin D
AU  - Schneider, Linda
AU  - Lunnebach, Jonah E
AU  - Leven, Patrick
AU  - Glowka, Tim R
AU  - Oberländer, Kristin
AU  - De Domenico, Elena
AU  - Schultze, Joachim L
AU  - Schmidt, Joachim
AU  - Kalff, Jörg C
AU  - Schneider, Anja
AU  - Wehner, Sven
AU  - Schneider, Reiner
TI  - Macrophage-induced enteric neurodegeneration leads to motility impairment during gut inflammation.
JO  - EMBO molecular medicine
VL  - 17
IS  - 2
SN  - 1757-4676
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2025-00315
SP  - 301 - 335
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Macrophages: metabolism
KW  - Humans
KW  - Mice
KW  - Gastrointestinal Motility
KW  - Enteric Nervous System: pathology
KW  - Enteric Nervous System: physiopathology
KW  - Disease Models, Animal
KW  - Inflammation: pathology
KW  - Neurons: pathology
KW  - Neurons: metabolism
KW  - Mice, Inbred C57BL
KW  - Male
KW  - Mice, Knockout
KW  - Enteric Neurons (Other)
KW  - Macrophages (Other)
KW  - Neuroimmune Interaction (Other)
KW  - Postoperative Ileus (Other)
KW  - Synaptic Damage (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39762650
C2  - pmc:PMC11822118
DO  - DOI:10.1038/s44321-024-00189-w
UR  - https://pub.dzne.de/record/276776
ER  -