Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats

Abstract

The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age.

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

“…It is well known that, like other cells, the number of ICCs is controlled by several factors that regulate proliferation and death and that ICCs continuously undergo apoptosis in the GI tract of healthy individuals [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Because neurons produce Stem Cell Factor (SCF), which activates the c-kit receptor and stimulates the proliferation, survival…”

“…Structural damage of the Enteric Nervous System (ENS), denervation above 90% in the myenteric plexus [7], ganglionitis and periganglionitis have been widely described in the digestive form of Chagas disease [8,9]. It is well known, however, that motility regulation in the GI tract and lower esophageal sphincter relaxation is influenced not only by neuromediators, as Nitric Oxide (NO), but also by Interstitial Cells of Cajal (ICCs) [10][11][12][13]. ative decrease in the number of neurons in colon of chagasic patient with megacolon [25].…”

Correction: Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats

“…Kwon YH, Kim N, Nam RH, Park JH, Lee SM, Kim SK, et al (2017) Correction: Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats. PLoS ONE 12(6): e0179107.…”

Hypoganglionosis in the gastric antrum causes delayed gastric emptying

“…The underlying pathophysiology of this observation is complex, with the enteric nervous system (ENS) thought to play a major role. Changes in the size and appearance of myenteric ganglia, and alterations of ICCs with age have been reported in the stomach and in the small and large intestine of experimental animals and humans . Abnormalities in enteric neuronal subtypes have been found to be associated with these changes.…”