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000276776 1001_ $$aBreßer, Mona$$b0
000276776 245__ $$aMacrophage-induced enteric neurodegeneration leads to motility impairment during gut inflammation.
000276776 260__ $$a[London]$$bNature Publishing Group UK$$c2025
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000276776 520__ $$aCurrent studies pictured the enteric nervous system and macrophages as modulators of neuroimmune processes in the inflamed gut. Expanding this view, we investigated the impact of enteric neuron-macrophage interactions on postoperative trauma and subsequent motility disturbances, i.e., postoperative ileus. In the early postsurgical phase, we detected strong neuronal activation, followed by transcriptional and translational signatures indicating neuronal death and synaptic damage. Simultaneously, our study revealed neurodegenerative profiles in macrophage-specific transcriptomes after postoperative trauma. Validating the role of resident and monocyte-derived macrophages, we depleted macrophages by CSF-1R-antibodies and used CCR2-/- mice, known for reduced monocyte infiltration, in POI studies. Only CSF-1R-antibody-treated animals showed decreased neuronal death and lessened synaptic decay, emphasizing the significance of resident macrophages. In human gut samples taken early and late during abdominal surgery, we substantiated the mouse model data and found reactive and apoptotic neurons and dysregulation in synaptic genes, indicating a species' overarching mechanism. Our study demonstrates that surgical trauma activates enteric neurons and induces neurodegeneration, mediated by resident macrophages, introducing neuroprotection as an option for faster recovery after surgery.
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000276776 650_7 $$2Other$$aEnteric Neurons
000276776 650_7 $$2Other$$aMacrophages
000276776 650_7 $$2Other$$aNeuroimmune Interaction
000276776 650_7 $$2Other$$aPostoperative Ileus
000276776 650_7 $$2Other$$aSynaptic Damage
000276776 650_2 $$2MeSH$$aAnimals
000276776 650_2 $$2MeSH$$aMacrophages: metabolism
000276776 650_2 $$2MeSH$$aHumans
000276776 650_2 $$2MeSH$$aMice
000276776 650_2 $$2MeSH$$aGastrointestinal Motility
000276776 650_2 $$2MeSH$$aEnteric Nervous System: pathology
000276776 650_2 $$2MeSH$$aEnteric Nervous System: physiopathology
000276776 650_2 $$2MeSH$$aDisease Models, Animal
000276776 650_2 $$2MeSH$$aInflammation: pathology
000276776 650_2 $$2MeSH$$aNeurons: pathology
000276776 650_2 $$2MeSH$$aNeurons: metabolism
000276776 650_2 $$2MeSH$$aMice, Inbred C57BL
000276776 650_2 $$2MeSH$$aMale
000276776 650_2 $$2MeSH$$aMice, Knockout
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000276776 7001_ $$aSiemens, Kevin D$$b1
000276776 7001_ $$aSchneider, Linda$$b2
000276776 7001_ $$aLunnebach, Jonah E$$b3
000276776 7001_ $$00000-0002-6768-2523$$aLeven, Patrick$$b4
000276776 7001_ $$00000-0001-6996-9766$$aGlowka, Tim R$$b5
000276776 7001_ $$0P:(DE-2719)2812835$$aOberländer, Kristin$$b6$$udzne
000276776 7001_ $$0P:(DE-2719)9000846$$aDe Domenico, Elena$$b7
000276776 7001_ $$0P:(DE-2719)2811660$$aSchultze, Joachim L$$b8$$udzne
000276776 7001_ $$aSchmidt, Joachim$$b9
000276776 7001_ $$aKalff, Jörg C$$b10
000276776 7001_ $$0P:(DE-2719)2812035$$aSchneider, Anja$$b11$$udzne
000276776 7001_ $$00000-0002-8632-7631$$aWehner, Sven$$b12
000276776 7001_ $$0P:(DE-2719)9001240$$aSchneider, Reiner$$b13
000276776 773__ $$0PERI:(DE-600)2485479-7$$a10.1038/s44321-024-00189-w$$gVol. 17, no. 2, p. 301 - 335$$n2$$p301 - 335$$tEMBO molecular medicine$$v17$$x1757-4676$$y2025
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