Changes in Enteric Neurons of Small Intestine in a Rat Model of Irritable Bowel Syndrome with Diarrhea

Abstract

Background/AimsPhysical and/or emotional stresses are important factors in the exacerbation of symptoms in irritable bowel syndrome (IBS). Several lines of evidence support that a major impact of stress on the gastrointestinal tract occurs via the enteric nervous system. We aimed to evaluate histological changes in the submucosal plexus (SMP) and myenteric plexus (MP) of the distal ileum in concert with the intestinal motor function in a rat model of IBS with diarrhea. MethodsThe rat model was induced by heterotypic chronic and acute stress (CAS). The intestinal transit was measured by administering powdered carbon by gastric gavage. Double immunohistochemical fluorescence staining with whole-mount preparations of SMP and MP of enteric nervous system was used to assess changes in expression of choline acetyltransferase, vasoactive intestinal peptide, or nitric oxide synthase in relation to the pan neuronal marker, anti-Hu. ResultsThe intestinal transit ratio increased significantly from control values of 50.8% to 60.6% in the CAS group. The numbers of enteric ganglia and neurons in the SMP were increased in the CAS group. The proportions of choline acetyltransferase-and vasoactive intestinal peptide-immunoreactive neurons in the SMP were increased (82.1 ± 4.3% vs. 76.0 ± 5.0%, P = 0.021; 40.5 ± 5.9% vs 28.9 ± 3.7%, P = 0.001), while nitric oxide synthase-immunoreactive neurons in the MP were decreased compared with controls (23.3 ± 4.5% vs 32.4 ± 4.5%, P = 0.002). ConclusionsThese morphological changes in enteric neurons to CAS might contribute to the dysfunction in motility and secretion in IBS with diarrhea. (J Neurogastroenterol Motil 2016;22:310-320)

Role of High-affinity Choline Transporter 1 in Colonic Hypermotility in a Rat Model of Irritable Bowel Syndrome

“…A previous study has suggested that reduced proportion of nitrergic enteric neurons in the MP of the distal ileum contributes to the intestinal dysmotility observed in IBS. 31 However, our findings further demonstrate that intestinal dysmotility in IBS is also related to the hyperfunction of cholinergic neurons in the colonic MP. One potential explanation may be that chronic stress directly regulates the cholinergic system in ICCs and ENS via the brain-gut axis through key alterations in the expression and function of CHT1.…”

“…44 In addition, NOdependent neurotransmission can exert inhibitory function on the GI contractility to counteract the effects of the cholinergic system. 31 All of these facts suggest a complex role for CHT1 in the regulation of GI motility in IBS. More recently, a study demonstrated that CHT1 also regulates the enzyme activity of enhanced mucosal acetylcholinesterase and influences the release of ACh by affecting the mobilization of vesicle pools, in addition to serving as the choline transporter.…”

Stress, sex, and the enteric nervous system

“…30 Alterations in the structure and composition of the ENS have also been found in adult male rats exposed to 28 days of heterotypic chronic and acute stress which exhibit an increase in cholinergic and VIPergic neurons in ileal submucosal plexus, while in the myenteric plexus, the number of NOS-positive neurons is decreased. 31 In this issue, Medland et al 7 add to the existing literature by demonstrating for the first time using EWS that this effect is reproducible and longlasting in a larger mammalian species (pigs) which has translational relevance for humans. 8 Additionally, they show that there is a sex-specific hypersensitivity of secretomotor neuron function and upregulation of the cholinergic ENS which occurs in females exclusively.…”

Gene-environment interactions and the enteric nervous system: Neural plasticity and Hirschsprung disease prevention

“…Remarkably, early life emotional distress (e.g., maternal separation model) and adult stress (e.g. water immersion in rodents) can also cause long-term changes in enteric glia and neurons, as well as changes in colon and gastric function in ways that may be relevant for gastroparesis and IBS (Bian et al, 2011; Fujikawa et al, 2015; Li et al, 2015; Moloney et al, 2015; Tominaga et al, 2016). Non-genetic factors may also protect the ENS from injury.…”