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001     276776
005     20250216000803.0
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037 _ _ |a DZNE-2025-00315
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082 _ _ |a 610
100 1 _ |a Breßer, Mona
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245 _ _ |a Macrophage-induced enteric neurodegeneration leads to motility impairment during gut inflammation.
260 _ _ |a [London]
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|b Nature Publishing Group UK
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520 _ _ |a 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.
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650 _ 7 |a Enteric Neurons
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650 _ 7 |a Macrophages
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650 _ 7 |a Neuroimmune Interaction
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650 _ 7 |a Postoperative Ileus
|2 Other
650 _ 7 |a Synaptic Damage
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Macrophages: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Gastrointestinal Motility
|2 MeSH
650 _ 2 |a Enteric Nervous System: pathology
|2 MeSH
650 _ 2 |a Enteric Nervous System: physiopathology
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Inflammation: pathology
|2 MeSH
650 _ 2 |a Neurons: pathology
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
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650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice, Knockout
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773 _ _ |a 10.1038/s44321-024-00189-w
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