Abstract
The present study analysed changes in the distribution pattern of cocaine- and amphetamine-regulated transcript (CART) in the enteric nervous system (ENS) of the human colon challenged by adenocarcinoma invasion, using the double-labelling immunofluorescence technique. In control specimens, CART immunoreactivity was found in neurons of all studied plexuses, representing 30.1 ± 4.1%, 12.9 ± 5.2%, and 4.1 ± 1.3% of all neurons forming the myenteric plexus (MP), outer submucous plexus (OSP), and inner submucous plexus (ISP), respectively. Tumour growth into the colon wall caused an increase in the relative frequency of CART-like immunoreactive (CART-LI) neurons in enteric plexuses located in the vicinity of the infiltrating neoplasm (to 36.1 ± 6.7%, 32.7 ± 7.3% and 12.1 ± 3.8% of all neurons in MP, OSP and ISP, respectively). The density of CART-LI nerves within particular layers of the intestinal wall did not differ between control and adenocarcinoma-affected areas of the human colon. This is the first detailed description of the CART distribution pattern within the ENS during the adenocarcinoma invasion of the human colon wall. The obtained results suggest that CART probably acts as a neuroprotective factor and may be involved in neuronal plasticity evoked by the progression of a neoplastic process.
Highlights
It is well known that gastrointestinal (GI) activities are regulated both by the extrinsic innervation and the enteric nervous system (ENS) located in the wall of the GI tract [1,2]
Previous studies on the GI tract have described the numerous cocaine- and amphetamine-regulated transcript (CART)-immunoreactive neurons and nerve fibers in the myenteric plexus (MP) and circular muscle (CM) [20,21,22], which may suggest that CART is involved in the regulation of the intestinal motility and secretion
Recent studies show that CART expression in small bowel carcinoid tumours is associated with lower rates of patient survival [32]. These findings suggest the participation of CART in neuroprotective processes within the ENS and in conduction of sensory stimuli
Summary
It is well known that gastrointestinal (GI) activities are regulated both by the extrinsic innervation and the enteric nervous system (ENS) located in the wall of the GI tract [1,2]. Previous studies on the GI tract have described the numerous CART-immunoreactive neurons and nerve fibers in the MP and CM [20,21,22], which may suggest that CART is involved in the regulation of the intestinal motility and secretion It is relatively well-known that the ENS in the large intestine can undergo changes during the course of many diseases. It should be noted that the exact mechanisms of observed changes are difficult to explain, due to the fact that functions of CART in the GI tract are not fully understood It may be connected with direct damage to enteric neurons by neoplastic proliferation, pain stimuli conduction, or derivative disturbances in intestinal motility and excretive activity. CART potentially plays multiple functions in the large human intestine, both in physiological conditions and during carcinoma infiltration, but many aspects of its activity within the GI tract remain unknown and need further investigation
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