129999 20240118092026.0 doi 10.1111/nmo.14036 sideral 121642 ART-2020-121642 eng Marsilio, I. Oxidized phospholipids affect small intestine neuromuscular transmission and serotonergic pathways in juvenile mice 2020 Background 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. Access copy available to the general public Unrestricted info:eu-repo/semantics/openAccess All rights reserved http://www.europeana.eu/rights/rr-f/ 3.598 2020 CLINICAL NEUROLOGY 87 / 208 = 0.418 2020 Q2 T2 NEUROSCIENCES 139 / 273 = 0.509 2020 Q3 T2 GASTROENTEROLOGY & HEPATOLOGY 56 / 92 = 0.609 2020 Q3 T2 1.489 2020 Endocrine and Autonomic Systems 2020 Q1 Physiology 2020 Q1 Gastroenterology 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion Caputi, V. Latorre, E. Universidad de Zaragoza (orcid)0000-0002-5797-3909 Cerantola, S. Paquola, A. Alcalde, A.I. (orcid)0000-0002-9935-927X Mesonero, J.E. Universidad de Zaragoza (orcid)0000-0003-4758-3998 O'Mahony, S.M. Bertazzo, A. Giaroni, C. Giron, M.C. 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 33, 4 (2020), e14036 [14 pp] Neurogastroenterol. motil. NEUROGASTROENTEROLOGY AND MOTILITY 1350-1925 2377795 http://zaguan.unizar.es/record/129999/files/texto_completo.pdf Postprint 1192865 http://zaguan.unizar.es/record/129999/files/texto_completo.jpg?subformat=icon icon Postprint oai:zaguan.unizar.es:129999 articulos driver 2024-01-18-09:05:06 ARTICLE