Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice

Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF-and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity

L'INU CONSULENTE DELLA REGIONE BASILICATA

Il testo contiene un primo resoconto delle attività di consulenza dell'INU alla Regione Basilicata (coordinate da A. Filpa e W. Fabietti) per l'attuazione di programmi integrati ex L. 179/9

I PROGRAMMI INTEGRATI DEL VULTURE

Il testo affronta, con riferimento alla esperienza compiuta dalla Regione Basilicata (con consulenza INU; coordinatori W. Fabietti e A. Filpa), le problematiche inerenti l’applicazione dei modelli valutativi alle trasformazioni urbane, evidenziando l’impatto amministrativo delle procedure di valutazione nonchè i fattori di successo ed i limiti delle procedure stesse

L'ATTIVITA' DI CONSULENZA DELL'INU E GLI ESITI DEL COORDINAMENTO REGIONALE

Il testo contiene un resoconto dei risultati della attività di consulenza svolta dall’INU alla Regione Basilicata

COME COLLEGARE LA PIANIFICAZIOE TERRITORIALE CON LA CONSERVAZIONE DELLA BIODIVERSITA' E L'ECODIVERSITA' DEL PAESAGGIO

iL CONTRIBUTO ESPLORA LE POSSIBILI INTERRELAZIONI TRA PIANIFICAZIONE DI MATRICE TERRITORIALE CON LA TUTELA DEL PAESAGGIO E DELLA BIODIVERSITA

Interaction between NMDA glutamatergic and nitrergic enteric pathways during in vitro ischaemia and reperfusion

Nitric oxide (NO) and glutamate, via N-methyl-D-aspartate (NMDA) receptors, participate to changes in neuromuscular responses after ischemic/reperfusion (I/R) injury in the gut. In the present study we investigated the existence of a possible interplay between nitrergic and NMDA receptor pathways in the guinea pig ileum after in vitro I/R injury, resorting to functional and biomolecular approaches. In normal metabolic conditions NMDA concentration-dependently enhanced both glutamate (analysed by high performance liquid chromatography with fluorimetric detection) and NO (spectrophotometrically quantified as NO2- and NO3-) spontaneous overflow from isolated ileal segments. Both effects were reduced by the NMDA antagonists, (-)-AP5 (10 \ub5M) and 5,7-diCl-kynurenic acid (10 \ub5M, 5,7-diCl-KYN). N\u3c9-propyl-L-arginine (1 \ub5M, NPLA) and 1400W (10 \ub5M), respectively, nNOS and iNOS inhibitors, reduced NMDA-stimulated glutamate overflow. After in vitro I/R, glutamate overflow increased, and returned to control values in the presence of NPLA and 1400W. NO2- and NO3- levels transiently increased during I/R and were reduced by both (-)-AP5 and 5,7-diCl-KYN. In longitudinal muscle myenteric plexus preparations, iNOS mRNA and protein levels increased after in vitro I/R; both parameters were reduced to control values by (-)-AP5 and 5,7-diCl-KYN. Both antagonists were also able to reduce ischaemia-induced enhancement of nNOS mRNA levels. Protein levels of GluN1, the ubiquitary subunit of NMDA receptors, increased after I/R and were reduced by both NPLA and 1400W. On the whole, this data suggests the existence of a cross-talk between NMDA receptor and nitrergic pathways in guinea pig ileum myenteric plexus, which may participate to neuronal rearrangements occurring during I/R

nELAV mRNA- binding protein, HuC/D alteration in adolescent mice small intestine after antibiotic treatment- induced dysbiosis

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Impact of antibiotic-induced microbiota depletion on small bowel excitatory and inhibitory neuromuscular pathways in adolescent mice.

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