Changes in Interstitial Cells of Cajal at the Deep Muscular Plexus Are Associated with Loss of Distention-Induced Burst-Type Muscle Activity in Mice Infected by Trichinella spiralis

Abstract

The physiology and pathophysiology of the network of interstitial cells of Cajal associated with the deep muscular plexus (ICC-DMP) of the small intestine are still poorly understood. The objectives of the present study were to evaluate the effects of inflammation associated with Trichinella spiralis infection on the ICC-DMP and to correlate loss of function with structural changes in these cells and associated structures. We used immunohistochemistry, electron microscopy, and assessment of distention-inducing electrophysiological parameters in vitro. Damage to ICC-DMP was associated with a loss of distention-induced patterns of electrical activity normally associated with distention-induced peristalsis. Consistently, the timing of recovery of ICC-DMP paralleled the timing of recovery of the distention-induced activity. Nerve varicosities associated with ICC-DMP including cholinergic nerves, assessed by immunoelectron microscopy and whole mount double labeling, paralleled injury to ICC-DMP thus contributing to impaired excitatory innervation of smooth muscle cells. Major additional changes included a remodeling of the inner circular muscle layer, which may affect long-term sensitivity to distention after infection. In conclusion, transient injury to ICC-DMP in response to T. spiralis infection is severe and associated with a complete lack of distention-induced burst-type muscle activity.

Neurotensin Changes Propulsive Activity into a Segmental Motor Pattern in the Rat Colon

“…43 Potential stimuli are not limited to neurotransmitters; fatty acids such as butyrate and decanoic acid can also evoke the low frequency pacemaker activity, 34 and so can distention. 44 Siegle and Ehrlein's observation that neurotensin can evoke segmentation can be explained by the induction of ICC-DMP pacemaker activity. 41 The segmentation motor pattern in the mouse intestine can be inhibited by TTX or it can be prominently present after blocking neural activity.…”

Co-regulated Intestinal c-kit by Interleukin-17 and Interleukin-10 on Post-infectious Irritable Bowel Syndrome in Mice

“…Decreased IL-10 levels and uncontrolled IL-17 in this study may hold a low-grade inflammation mode undetected by pathological examination [22,31]. Meanwhile, mucosal acute inflammation of the gut resulted in loss of ICC function because of structural injury and loss of c-kit positivity [32]. When the low-grade inflammation was not enough to cause tissue damage but could result in mild cell injury, inflammatory cytokines can act as stimulating factors to improve protein synthesizing just like inflammatory hyperplasia and autoimmunity disease, in this moment, the rough endoplasmic reticulum and Golgi apparatus of the injury ICC need to synthesize proteins (including c-kit) to form new plasma membrane and to recover structure and functions [32].…”

“…Meanwhile, mucosal acute inflammation of the gut resulted in loss of ICC function because of structural injury and loss of c-kit positivity [32]. When the low-grade inflammation was not enough to cause tissue damage but could result in mild cell injury, inflammatory cytokines can act as stimulating factors to improve protein synthesizing just like inflammatory hyperplasia and autoimmunity disease, in this moment, the rough endoplasmic reticulum and Golgi apparatus of the injury ICC need to synthesize proteins (including c-kit) to form new plasma membrane and to recover structure and functions [32]. Overexpressed c-kit is required for development and maintenance of ICC, also is necessary for development of coordinated motility patterns and for survival of ICC [7,8].…”

Bone Marrow Derived Kit-positive Cells Colonize the Gut but Fail to Restore Pacemaker Function in Intestines Lacking Interstitial Cells of Cajal

“…ICC restoration has been observed in a variety of models including chemical lesion, 36,39 surgical lesion 15,16 and inflammation. 47 In these studies ICC networks were disrupted following the pathophysiological insult but restoration of functional ICC networks occurred upon removal of the insult. Although ICC possess a degree of plasticity, the mechanism of how they repopulate GI tissues is controversial.…”