000129999 001__ 129999
000129999 005__ 20240118092026.0
000129999 0247_ $$2doi$$a10.1111/nmo.14036
000129999 0248_ $$2sideral$$a121642
000129999 037__ $$aART-2020-121642
000129999 041__ $$aeng
000129999 100__ $$aMarsilio, I.
000129999 245__ $$aOxidized phospholipids affect small intestine neuromuscular transmission and serotonergic pathways in juvenile mice
000129999 260__ $$c2020
000129999 5060_ $$aAccess copy available to the general public$$fUnrestricted
000129999 5203_ $$aBackground
Oxidized phospholipid derivatives (OxPAPCs) act as bacterial lipopolysaccharide (LPS)-like damage-associated molecular patterns. OxPAPCs dose-dependently exert pro- or anti-inflammatory effects by interacting with several cellular receptors, mainly Toll-like receptors 2 and 4. It is currently unknown whether OxPAPCs may affect enteric nervous system (ENS) functional and structural integrity.
Methods
Juvenile (3 weeks old) male C57Bl/6 mice were treated intraperitoneally with OxPAPCs, twice daily for 3 days. Changes in small intestinal contractility were evaluated by isometric neuromuscular responses to receptor and non-receptor-mediated stimuli. Alterations in ENS integrity and serotonergic pathways were assessed by real-time PCR and confocal immunofluorescence microscopy in longitudinal muscle-myenteric plexus whole-mount preparations (LMMPs). Tissue levels of serotonin (5-HT), tryptophan, and kynurenine were measured by HPLC coupled to UV/fluorescent detection. Key
Results
OxPAPC treatment induced enteric gliosis, loss of myenteric plexus neurons, and excitatory hypercontractility, and reduced nitrergic neurotransmission with no changes in nNOS(+) neurons. Interestingly, these changes were associated with a higher functional response to 5-HT, altered immunoreactivity of 5-HT receptors and serotonin transporter (SERT) together with a marked decrease in 5-HT levels, shifting tryptophan metabolism toward kynurenine production.
Conclusions and Inferences
OxPAPC treatment disrupted structural and functional integrity of the ENS, affecting serotoninergic tone and 5-HT tissue levels toward a higher kynurenine content during adolescence, suggesting that changes in intestinal lipid metabolism toward oxidation can affect serotoninergic pathways, potentially increasing the risk of developing functional gastrointestinal disorders during critical stages of development.
000129999 540__ $$9info:eu-repo/semantics/openAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000129999 590__ $$a3.598$$b2020
000129999 591__ $$aCLINICAL NEUROLOGY$$b87 / 208 = 0.418$$c2020$$dQ2$$eT2
000129999 591__ $$aNEUROSCIENCES$$b139 / 273 = 0.509$$c2020$$dQ3$$eT2
000129999 591__ $$aGASTROENTEROLOGY & HEPATOLOGY$$b56 / 92 = 0.609$$c2020$$dQ3$$eT2
000129999 592__ $$a1.489$$b2020
000129999 593__ $$aEndocrine and Autonomic Systems$$c2020$$dQ1
000129999 593__ $$aPhysiology$$c2020$$dQ1
000129999 593__ $$aGastroenterology$$c2020$$dQ1
000129999 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/acceptedVersion
000129999 700__ $$aCaputi, V.
000129999 700__ $$0(orcid)0000-0002-5797-3909$$aLatorre, E.$$uUniversidad de Zaragoza
000129999 700__ $$aCerantola, S.
000129999 700__ $$aPaquola, A.
000129999 700__ $$0(orcid)0000-0002-9935-927X$$aAlcalde, A.I.
000129999 700__ $$0(orcid)0000-0003-4758-3998$$aMesonero, J.E.$$uUniversidad de Zaragoza
000129999 700__ $$aO'Mahony, S.M.
000129999 700__ $$aBertazzo, A.
000129999 700__ $$aGiaroni, C.
000129999 700__ $$aGiron, M.C.
000129999 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000129999 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000129999 773__ $$g33, 4 (2020), e14036 [14 pp]$$pNeurogastroenterol. motil.$$tNEUROGASTROENTEROLOGY AND MOTILITY$$x1350-1925
000129999 8564_ $$s2377795$$uhttps://zaguan.unizar.es/record/129999/files/texto_completo.pdf$$yPostprint
000129999 8564_ $$s1192865$$uhttps://zaguan.unizar.es/record/129999/files/texto_completo.jpg?subformat=icon$$xicon$$yPostprint
000129999 909CO $$ooai:zaguan.unizar.es:129999$$particulos$$pdriver
000129999 951__ $$a2024-01-18-09:05:06
000129999 980__ $$aARTICLE