title: Role of corticosterone in the murine enteric nervous system during fasting.
abstract: Food intake depends on a tightly controlled interplay of appetite hormones and the enteric (ENS) and central nervous system. Corticosterone (CORT) levels, which are mainly studied with regard to stress, are also increased during fasting. However, the role of CORT in the ENS remains elusive. Therefore, we investigated whether CORT modulates activity of enteric neurons and whether its intracellular regulator, 11β-hydroxysteroid dehydrogenase (HSD) type 1, is present in the myenteric plexus, using immunohistochemistry and RT-qPCR. Effects of CORT on neuronal activity and expression of neuronal markers in the myenteric plexus were assessed via Ca(2+) imaging and RT-qPCR, respectively, whereas modulations in mixing behavior were measured by video imaging. 11β-HSD-1 was present in enteric neurons along the gastrointestinal tract, and its expression increased after fasting (control: 0.58 ± 0.09 vs. fasted: 1.5 ± 0.23; P < 0.05). CORT incubation significantly reduced neuronal Ca(2+) transients in tissues stimulated by electrical pulses (control: 1.31 ± 0.01 vs. CORT: 1.27 ± 0.01, P < 0.01) and in cultured neurons (control: 1.85 ± 0.03 vs. CORT: 1.76 ± 0.03, P < 0.05). CORT decreased small intestinal mixing (P < 0.05). Incubation of muscle myenteric plexus preparations with CORT induced an increase in cannabinoid receptor 1 (CB1, P < 0.05) and synaptobrevin (P < 0.05) but not in 11β-HSD-1 mRNA expression. In addition, fasting induced significant elevations in synaptobrevin (P < 0.05) and CB1 (P < 0.01) mRNA expression. In conclusion, we suggest CORT to be a downstream factor in a feeding state-related pathway that modulates important proteins in the fine tuning of enteric neurotransmission and gastrointestinal motility.
authors.affiliation: Laboratory for Enteric NeuroScience, University of Leuven, Leuven, Belgium; and Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Lowette
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: Laboratory for Enteric NeuroScience, University of Leuven, Leuven, Belgium; and Translational Research Center for Gastrointestinal Disorders, University of Leuven, Leuven, Belgium pieter.vandenberghe@med.kuleuven.be.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vanden Berghe
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism; D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003345:Corticosterone / Q000097:blood* / Q000494:pharmacology; D005215:Fasting; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D050683:R-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism
chemical_list: D050683:R-SNARE Proteins; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D002118:Calcium; D003345:Corticosterone
keywords: appetite; neuromodulation