W1932 Melatonin Supplementation Suppresses Serotonin and Melatonin Availability in Aged Mouse Intestine

Abstract

Purpose: Aging is associated with important changes in gastrointestinal function and in the levels of intestinal hormones secreted. Enterochromaffin cells containing serotonin (5-HT) and melatonin may play a major role in maintaining gut function during aging. Our aim was to characterise the mucosal availability of 5-HT and melatonin in the ileum and colon of a mouse model of aging. Methods: Female young mice (2-5 month; n=6), aged mice (~21 months; n=6) and aged mice treated with melatonin (~21 months; n=6; 10mg/kg/day) were examined. Electrochemical methods were used to measure 5-HT and melatonin (MEL) concentrations near the mucosal surface of ileum and distal colon. Amperometry was used to record compression evoked 5-HT while cyclic voltammetry was used to identify peaks for 5-HT and MEL. Differential pulse voltammetry (DPV: 500/800mV) was used to measure 5-HT and MEL steady state levels. Exogenous 5-HT and MEL were used to calibrate the carbon fibre electrodes and convert current into concentration. Paired or unpaired data were compared with a t test or a one way ANOVA (P<0.05) using a Tukey-Kramer post-hoc test. Results: Amperometry studies showed that young mice had peak compression evoked release of 5-HT from combined colon and ileum of 4.9±1.5 μM while aged mice had a enhanced release of 8.1±2.9 μM and aged mice treated with melatonin were significally depressed compared to aged mice (4.3±1.0 μM; P=004). Steady state levels of 5-HT after compression from combined tissue were 5.7±1.8 μM in young tissue while aged mice (4.8±0.6 μM) and aged mice treated with melatonin were no different from young mice (3.2±0.6 μM). DPV studies showed that young mice had concentrations of 5-HT of 4.1±1.1 μM in the ileum and 5.9±2.4 μM in the colon. Concentrations of MEL were 5.3±1.6 μM in the ileum and 4.7±1.5 μM in the colon (all n=6). Compared to young mice, the steady state levels of 5HT and MEL were increased in aged mice (combined ileum and colon: 5-HT=144% and MEL=127% of young mice). In contrast, the melatonin-treated mice had lower steady state levels compared to young mice (5-HT=89% andMEL=74%).When aged mice were compared directly with aged mice treated with melatonin, there was a significant decrease in both 5HT and MEL in the treated combined tissues (P=0.001); however, when ileum and colon were examined separately only MEL was significantly decreased in the ileum (P=0.04; n= 6) and colon (P=0.02; n=6) of treated mice. Conclusions: Our data show that the availability of 5-HT and melatonin are increased in aged mice and that melatonin treatment suppresses natural gastrointestinal production of 5-HT and melatonin in the aged mouse intestine.