Oxidized phospholipids affect small intestine neuromuscular transmission and serotonergic pathways in juvenile mice

Marsilio, I. ; Caputi, V. ; Latorre, E. (Universidad de Zaragoza) ; Cerantola, S. ; Paquola, A. ; Alcalde, A.I. ; Mesonero, J.E. (Universidad de Zaragoza) ; O'Mahony, S.M. ; Bertazzo, A. ; Giaroni, C. ; Giron, M.C.

Resumen: 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.

Idioma: Inglés

DOI: 10.1111/nmo.14036

Año: 2020

Publicado en: NEUROGASTROENTEROLOGY AND MOTILITY 33, 4 (2020), e14036 [14 pp]
ISSN: 1350-1925

Factor impacto JCR: 3.598 (2020)

Categ. JCR: CLINICAL NEUROLOGY rank: 87 / 208 = 0.418 (2020) - Q2 - T2
Categ. JCR: NEUROSCIENCES rank: 139 / 273 = 0.509 (2020) - Q3 - T2
Categ. JCR: GASTROENTEROLOGY & HEPATOLOGY rank: 56 / 92 = 0.609 (2020) - Q3 - T2

Factor impacto SCIMAGO: 1.489 - Endocrine and Autonomic Systems (Q1) - Physiology (Q1) - Gastroenterology (Q1)

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)