Cocaine and Amphetamine Regulated Transcript (CART) Expression Changes in the Stomach Wall Affected by Experimentally Induced Gastric Ulcerations.

Michal Zalecki,Hanna Antushevich,Amelia Franke-Radowiecka,Adrianna Plywacz

doi:10.3390/ijms22147437

Abstract

Cocaine- and amphetamine-regulated transcript (CART) is a peptide suggested to play a role in gastrointestinal tract tissue reaction to pathology. Gastric ulceration is a common disorder affecting huge number of people, and additionally, it contributes to the loss of pig livestock production. Importantly, ulceration as a focal disruption affecting deeper layers of the stomach wall differs from other gastrointestinal pathologies and should be studied individually. The pig’s gastrointestinal tract, due to its many similarities to the human counterpart, provides a valuable experimental model for studying digestive system pathologies. To date, the role of CART in gastric ulceration and the expression of the gene encoding CART in porcine gastrointestinal tube are completely unknown. Therefore, we aimed to verify the changes in the CART expression by Q-PCR (gene encoding CART in the tissue) and double immunofluorescence staining combined with confocal microscopy (CART immunofluorescence in enteric nervous system) in the porcine stomach tissues adjacent to gastric ulcerations. Surprisingly, we found that gastric ulcer caused a significant decrease in the expression of CART-encoding gene and huge reduction in the percentage of CART-immunofluorescent myenteric perikarya and neuronal fibers located within the circular muscle layer. Our results indicate a unique CART-dependent gastric response to ulcer disease.

Highlights

Cocaine- and amphetamine-regulated transcript (CART), a relatively recently discovered peptide, is being recognized as a substance playing an important role in the peripheral nervous system and is known to be expressed in nerves supplying various organs, especially the digestive tract
Microscopic analysis revealed that in all studied animals CART-immunofluorescence was observed mainly in the myenteric perikarya (Figure 1A–D) and nerve fibers located within muscular layer (Figure 1E,G), while only occasional irregularly arranged submucosal perikarya were noticed in a few individuals of both animal groups (Figure 2A–D) and no difference in their occurrence and number was noticed
Results of the Q-PCR revealed the expression of gene encoding CART in the stomach of the Q-PCR

Summary

Introduction

Cocaine- and amphetamine-regulated transcript (CART), a relatively recently discovered peptide, is being recognized as a substance playing an important role in the peripheral nervous system and is known to be expressed in nerves supplying various organs, especially the digestive tract. As a part of the digestive tract, is widely innervated by extrinsic and intrinsic nerves, and the later form a complicated and highly autonomic enteric nervous system [1]. Multiple experiments have revealed the reaction of enteric neurons to pathology, which was manifested by changes in expression of different neuropeptides by intrinsic nerve cells [2]. It should be stressed, that gastrointestinal tissue and nerve reactions are highly specific and strongly dependent on the influencing factor and the part of the intestinal tube [1,2]. The only available studies verified the changes in CART-immunoreactive stomach neurons during experimentally induced diabetes mellitus type I [11], intoxication with T2 toxin [12], acrylamide [13], and bisphenol a [14]

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