Alterations in the jejunal 5-hydroxytryptamine synthesis and turnover in septic mice induced by cecal ligation and puncture.

Abstract

Recent studies have shown that endogenous 5-hydroxytryptamine (5-HT) facilitates in the progression of sepsis pathology. We aimed to characterize the impact of sepsis induced by cecal ligation and puncture (CLP) surgery on 5-HT synthesis and the metabolic system in mice jejunum at multiple pathological stages. The jejunal tissue were isolated at 3, 6, 12, 24 and 48 h after the surgical procedure of CLP. We found that the sepsis induced by the CLP procedure leads to significant body weight loss and intestinal injury, including villus atrophy associated with pro-inflammatory cytokine expression. We also demonstrated that sepsis alters intestinal 5-HT synthesis and degradation at distinct phases, an increase in 5-hydroxyindoleacetic acid, a final metabolite of 5-HT, at 3-6 h and a rise in 5-HT levels at 24 h. Tryptophan hydroxylase 1 and serotonin transporter expression increased at specific time points following CLP procedure. Additionally, MAO-A protein expression showed a rise at 12 h, while MAO activity significantly suppressed between 12 and 48 h. These findings offer valuable insight into the regulation of 5-HT synthesis and degradation at various stages of sepsis, potentially informing therapeutic strategies aimed at modulating 5-HT metabolism.