Τρίτη 5 Ιουλίου 2016

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

Abstract

Background

Nesfatin-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.

Methods

An 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 Results

Rats 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 & Inferences

Elevated 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.

Thumbnail image of graphical abstract

This study provides novel evidence that nesfatin-1 in the amygdala may participate in the pathophysiology of IBS-like visceral hypersensitivity, which may be mediated, at least in part, by GR and MR signaling.



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