Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

What is the central question of this study? What are the effects of interstitial cells of Cajal (ICC) network perturbations on intestinal pacemaker activity and motor patterns? What is the main finding and its importance? Two-dimensional modelling of the ICC pacemaker activity according to a phase model of weakly coupled oscillators showed that network properties (coupling strength between oscillators, frequency gradient and frequency noise) strongly influence pacemaker network activity and subsequent motor patterns. The model explains motor patterns observed in physiological conditions and provides predictions and testable hypotheses for effects of ICC loss and frequency modulation on the motor patterns. Interstitial cells of Cajal (ICC) are the pacemaker cells of gut motility and are associated with motility disorders. Interstitial cells of Cajal form a network, but the contributions of its network properties to gut physiology and dysfunction are poorly understood. We modelled an ICC network as a two-dimensional network of weakly coupled oscillators with a frequency gradient and showed changes over time in video and graphical formats. Model parameters were obtained from slow-wave-driven contraction patterns in the mouse intestine and pacemaker slow-wave activities from the cat intestine. Marked changes in propagating oscillation patterns (including changes from propagation to non-propagating) were observed by changing network parameters (coupling strength between oscillators, the frequency gradient and frequency noise), which affected synchronization, propagation velocity and occurrence of dislocations (termination of an oscillation). Complete uncoupling of a circumferential ring of oscillators caused the proximal and distal section to desynchronize, but complete synchronization was maintained with only a single oscillator connecting the sections with high enough coupling. The network of oscillators could withstand loss; even with 40% of oscillators lost randomly within the network, significant synchronization and anterograde propagation remained. A local increase in pacemaker frequency diminished anterograde propagation; the effects were strongly dependent on location, frequency gradient and coupling strength. In summary, the model puts forth the hypothesis that fundamental changes in oscillation patterns (ICC slow-wave activity or circular muscle contractions) can occur through physiological modulation of network properties. Strong evidence is provided to accept the ICC network as a system of coupled oscillators.

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“…We need to establish a possible association between disease severity and the extent of reduction of ICC (Yin & Chen, ; Araujo et al . ).…”

Section: Introductionmentioning

confidence: 97%

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators

Wei

Parsons

Huizinga

2017

Experimental Physiology

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“…Actually, several studies, although not all, have provided evidence that patients with primary achalasia, whose symptoms are fairly similar as compared with those observed in the chagasic form, show functional autonomic nervous system disturbances (vagal impairment) [39][40][41][42] . Besides degeneration and decreased numbers of intrinsic myenteric neurons, reduced numbers of intersticial cells of Cajal 14,43,44 and glial cells 14,22,45 , hypertrophic smooth cells, and increased fibrosis have also been reported, suggesting a complex physiopathology of chagasic esophageal and colonic disorders.…”

Section: Anti-m2r Antibodies In Chronic Chd Patients With Achalasia Amentioning

confidence: 99%

Gastrointestinal involvement in Chagas disease

Bilder¹,

Goin²

2018

NGL

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Achalasia and megacolon are the second most common manifestations of chronic Chagas disease (ChD) in endemic areas of Central and South America. Twenty or even more years after the initial infection, approximately one-third of infected people develop cardiac and/ or gastrointestinal abnormalities as typical chronic damages of ChD. The chronic phase of ChD is characterized by the damage of myenteric (intrinsic) and autonomic (extrinsic) neurons. A decreased density of enteric glial cells can be detected in patients with megaesophagus and megacolon and a loss of interstitial cells of Cajal. These lesions affect the complex mechanisms of neural, molecular, and cellular interactions that modulate the motor activity and other specific functions of the alimentary tract. Evidence for serum antibodies with the ability to recognize similar epitopes in both Trypanosoma cruzi and host antigens suggested that molecular mimicry could play a substantial role in the pathophysiology of chronic ChD. In fact, a high prevalence of circulating antibodies against M2 acetylcholine muscarinic receptor (M2R) in ChD patients with achalasia and megacolon has been found. These antibodies bind to and activate M2R, exhibiting agonist-like activity. Anti-M2R antibodies can both enhance tonic contraction in lower esophagus and distal colon by direct stimulation and also by counteracting the relaxant effect of drugs that increase cAMP accumulation (i.e. beta-adrenergic agonists). The biochemical and functional effects of these antibodies on esophageal and colon smooth muscle could play an important role in the pathophysiology of achalasia and megacolon secondary to ChD.

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Depopulation of interstitial cells of cajal in chagasic megacolon: towards tailored surgery?

Cited by 2 publications

References 23 publications

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators

Network properties of interstitial cells of Cajal affect intestinal pacemaker activity and motor patterns, according to a mathematical model of weakly coupled oscillators

Gastrointestinal involvement in Chagas disease

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