Role of corticosterone in the murine enteric nervous system during fasting

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, 11 beta-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 Ca2+ imaging and RT-qPCR, respectively, whereas modulations in mixing behavior were measured by video imaging. 11 beta-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 Ca2+ 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 11 beta-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.