Interstitial Cells of Cajal and Enteric Nervous System in Gastrointestinal and Neurological Pathology, Relation to Oxidative Stress

Abstract

The enteric nervous system (ENS) is organized into two plexuses—submucosal and myenteric—which regulate smooth muscle contraction, secretion, and blood flow along the gastrointestinal tract under the influence of the rest of the autonomic nervous system (ANS). Interstitial cells of Cajal (ICCs) are mainly located in the submucosa between the two muscle layers and at the intramuscular level. They communicate with neurons of the enteric nerve plexuses and smooth muscle fibers and generate slow waves that contribute to the control of gastrointestinal motility. They are also involved in enteric neurotransmission and exhibit mechanoreceptor activity. A close relationship appears to exist between oxidative stress and gastrointestinal diseases, in which ICCs can play a prominent role. Thus, gastrointestinal motility disorders in patients with neurological diseases may have a common ENS and central nervous system (CNS) nexus. In fact, the deleterious effects of free radicals could affect the fine interactions between ICCs and the ENS, as well as between the ENS and the CNS. In this review, we discuss possible disturbances in enteric neurotransmission and ICC function that may cause anomalous motility in the gut.

Colonic Electrical Stimulation for Chronic Constipation: A Perspective Review

“…The relationship between enteric nerves and ICCs is still under investigation [ 31 ]. It becomes evident that there are still numerous unresolved questions, showing the need for further research to understand deeply the neurophysiology of the colon.…”

NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation

“…This condition disrupts glycemic regulation and severely affects life quality [171]. Diabetic gastroparesis's origin involves OS, inflammation, and loss of gastric ICCs crucial for modulating gastric movement [172,173]. ICCs, specialized cells in the gastrointestinal system, regulate gut motility and coordinate smooth muscle contractions [174].…”

Pathophysiological Implications of Interstitial Cajal-like Cells (ICC-like) in Uterus: A Comparative Study with Gastrointestinal ICCs

“…Taking into account these three primary functions described above, it is understandable that changes in ICC numbers are associated with gastrointestinal motility disorders [ 14 ]. Several pathologies of childhood and old age have been associated with variations in the number of ICCs, as demonstrated by c-Kit immunolabeling.…”

“…Since ICCs have a central role in gastrointestinal peristalsis and enteric neurotransmission, their quantitative decrease may explain the motility dysfunction that occurs in this pediatric disease [ 15 ]. At older ages, a decrease in ICC numbers has been related to disorders such as acquired hypoganglionosis, diabetic or idiopathic gastroparesis, intestinal pseudo-obstruction, and chronic constipation [ 14 , 16 ]. Finally, and independently of age, megacolon associated with Chagas disease could also be explained by a lower density of ICCs.…”