Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice.
Animals
Anti-Bacterial Agents
/ adverse effects
Brain
/ metabolism
Brain-Derived Neurotrophic Factor
/ biosynthesis
Dysbiosis
/ chemically induced
Enteric Nervous System
/ metabolism
Gene Expression Regulation
/ drug effects
Irritable Bowel Syndrome
/ chemically induced
Membrane Glycoproteins
/ biosynthesis
Mice
Neurons
/ metabolism
Protein-Tyrosine Kinases
/ biosynthesis
Signal Transduction
/ drug effects
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
28
11
2018
accepted:
11
02
2019
entrez:
23
2
2019
pubmed:
23
2
2019
medline:
22
11
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30794676
doi: 10.1371/journal.pone.0212856
pii: PONE-D-18-34099
pmc: PMC6386304
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bdnf protein, mouse
0
Brain-Derived Neurotrophic Factor
0
Membrane Glycoproteins
0
Ntrk2 protein, mouse
EC 2.7.10.1
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0212856Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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