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J Neurogastroenterol Motil. 2017 Oct;23(4):592-605. English. Original Article. https://doi.org/10.5056/jnm17061
Lee SM , Kim N , Jo HJ , Park JH , Nam RH , Lee HS , Kim HJ , Lee MY , Kim YS , Lee DH .
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea. nayoungkim49@empas.com
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea.
Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Jinju, Gyeongsangnam-do, Korea.
Department of Physiology and Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Jeollabuk-do, Korea.
Division of Gastroenterology and Wonkwang Digestive Disease Research Institute, Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi-do, Korea.
Abstract

Background/Aims

Neuronal degeneration and changes in interstitial cells of Cajal (ICCs) are important mechanisms of age-related constipation. This study aims to compare the distribution of ICCs and neuronal nitric oxide synthase (nNOS) with regard to age-related changes between the ascending colon (AC) and descending colon (DC) in 6-, 31-, and 74-week old and 2-year old male Fischer-344 rats.

Methods

The amount of fecal pellet and the bead expulsion times were measured. Fat proportion in the muscle layer of the colon was analyzed by hematoxylin and eosin staining. Proto-oncogene receptor tyrosine kinase (KIT) and neuronal nitric oxide synthase (nNOS) expression were analyzed with Western blotting and immunohistochemistry. Isovolumetric contractile measurements and electrical field stimulation were used to assess smooth muscle contractility.

Results

Colon transit and bead expulsion slowed with senescence. Fat in the muscle layer accumulated with age in the AC, but not in the DC. The proportion of KIT-immunoreactive ICCs in the submucosal and myenteric plexus was higher in the DC than in the AC, and it declined with age, especially in the AC. In contrast, the proportion of NOS-immunoreactive neurons in the myenteric plexus was higher in the AC than in the DC, and both decreased in older rats. Nitric oxide levels declined with age in the DC. Muscle strip experiments showed that the inhibitory response mediated by nitric oxide in the circular direction of the DC was reduced in 2-year old rats.

Conclusion

The AC and DC differ in their distribution of ICCs and nNOS, and age-related loss of nitrergic neurons more severely affects the DC than the AC.

Copyright © 2019. Korean Association of Medical Journal Editors.