Nesfatin-1/NUCB2 in the amygdala influences visceral sensitivity via glucocorticoid and mineralocorticoid receptors in male maternal separation rats

作者：Zhou, X. -P.; Sha, J.; Huang, L.; Li, T. -N.^*; Zhang, R. -R.; Tang, M. -D.; Lin, L.; Li, X. -L.^*

来源：Neuro-Gastroenterology and Motility, 2016, 28(10): 1545-1553.

DOI：10.1111/nmo.12853

• amygdala
• irritable bowel syndrome
• maternal separation
• nesfatin-1
• visceral hypersensitivity

BackgroundNesfatin-1, a recently identified satiety molecule derived from nucleobindin 2 (NUCB2), is associated with visceral hypersensitivity in rats and is expressed in the amygdala. We tested the hypothesis that nesfatin-1 expression in the amygdala is involved in the pathogenesis of irritable bowel syndrome (IBS) visceral hypersensitivity. @@@ MethodsAn animal model of IBS-like visceral hypersensitivity was established using maternal separation (MS) during postnatal days 2-16. The role of nesfatin-1 in the amygdala on visceral sensitivity was evaluated. @@@ Key ResultsRats subjected to MS showed a significantly increased mean abdominal withdrawal reflex (AWR) score and electromyographic (EMG) activity at 40, 60, and 80 mmHg colorectal distension. Plasma concentrations of nesfatin-1 and corticosterone were significantly higher than in non-handled (NH) rats. mRNA and protein expression of nesfatin-1/NUCB2 in the amygdala were increased in MS rats, but not in NH rats. In MS rats, AWR scores and EMG activity were significantly decreased after anti-nesfatin-1/NUCB2 injection. In normal rats, mean AWR score, EMG activity, and corticosterone expression were significantly increased after nesfatin-1 injection into the amygdala. Nesfatin-1-induced visceral hypersensitivity was abolished following application of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) antagonists. @@@ Conclusions & InferencesElevated expression of nesfatin-1/NUCB2 in the amygdala in MS rats suggests a potential role in the pathogenesis of visceral hypersensitivity, which could potentially take place via activation of GR and MR signaling pathways.

• 出版日期2016-10
• 单位南京医科大学