J Neurogastroenterol Motil  
Comparison of Changes in the Interstitial Cells of Cajal and Neuronal Nitric Oxide Synthase-positive Neuronal Cells With Aging Between the Ascending and Descending Colon of F344 Rats
Sun Min Lee,1 Nayoung Kim,1,2* Hyun Jin Jo,1 Ji Hyun Park,2 Ryoung Hee Nam,1 Hye Seung Lee,3 Hyun Jin Kim,4 Moon Young Lee,5 Yong Sung Kim,6 and Dong Ho Lee1
1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
3Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do, Korea
4Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, Jinju, Gyeongsangnam-do, Korea
5Department of Physiology and Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Jeollabuk-do, Korea
6Division of Gastroenterology and Wonkwang Digestive Disease Research Institute, Department of Internal Medicine, Wonkwang University Sanbon Hospital, Gunpo, Gyeonggi-do, Korea
Correspondence to: Nayoung Kim, MD
Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 beon-gil, Bundang-gu, Seongnam, Gyeonggi-do 13620, Korea
Tel: + 82-31-787-7008, Fax: + 82-31-787-4051, E-mail: nayoungkim49@empas.com
Received: April 30, 2017; Revised: June 20, 2017; Accepted: July 9, 2017; Published online: August 4, 2017.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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. KIT protooncogene 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.
Keywords: Aging; Colon; Interstitial cells of Cajal; Nitric oxide synthase type I; Rats, inbred F344


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