Ultrastructural changes of the human
enteric nervous system and interstitial cells of Cajal in diverticular disease
Paulius Alaburda1, Jaune I. Lukosiene3, Audrys G. Pauza1*, Kristina Rysevaite-Kyguoliene1, Juozas Kupcinskas2,3, Zilvinas Saladzinskas4, Algimantas Tamelis4 and Neringa Pauziene1
1Institute of Anatomy, 2Institute for Digestive Research, 3Department of Gastroenterology and 4Department of Surgery, Lithuanian University of Health Sciences, Kaunas, Lithuania
*Present address: Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, United Kingdom
Offprint requests to: Neringa Pauziene, Insttute of Anatomy, Lithuanian University of Health Sciences, Kaunas, Kaunas apskritis, Lithuania. e-mail: firstname.lastname@example.org
Summary. Background. In spite of numerous advances in understanding diverticular disease, its pathogenesis remains one of the main problems to be solved. We aimed to investigate the ultrastructural changes of the enteric nervous system in unaffected individuals, in asymptomatic patients with diverticulosis and in patients with diverticular disease.
Methods. Transmission electron microscopy was used to analyse samples of the myenteric, outer submucosal and inner submucosal plexuses from patients without diverticula (n=9), asymptomatic patients with diverticulosis (n=7) and in patients with complicated diverticular disease (n=9). We described the structure of ganglia, interstitial cells of Cajal and enteric nerves, as well as their relationship with each other. The distribution and size of nerve processes were analysed quantitatively.
Results. In complicated diverticular disease, neurons exhibited larger lipofuscin-like inclusions, their membranous organelles had larger cisterns and the nucleus showed deeper indentations. Nerve remodeling occurred in every plexus, characterised by an increased percentage of swollen and fine neurites. Interstitial cells of Cajal had looser contacts with the surrounding cells and showed cytoplasmic depletion and proliferation of the rough endoplasmic reticulum. In asymptomatic patients with diverticulosis, alterations of enteric nerves and ICC were less pronounced.
Conclusions. In conclusion, the present findings suggest that most ultrastructural changes of the enteric nervous system occur in complicated diverticular disease. The changes are compatible with damage to the enteric nervous system and reactive remodeling of enteric ganglia, nerves and interstitial cells of Cajal. Disrupted architecture of enteric plexuses might explain clinical and pathophysiological changes associated with diverticular disease. Histol Histopathol 35, 147-157 (2020)
Key words: Diverticular disease, Colon, TEM, ENS, Interstitial cells of Cajal