Changes of the Different Neuropeptide‐Containing Nerve Fibers and Immunocells in the Diabetic Rat's Alimentary Tract

Abstract

Peripheral neuropathy is a common complication of diabetes mellitus, where neuropeptides and immunocells might play important roles in the pathogenesis of the disease. In this article we have quantified the different neuropeptide-containing nerve fibers and immunocells in the streptozotocin-induced diabetic rat's alimentary tract (tongue, duodenum, colon) using immunohistochemical and immunocytochemical methods. The immunoreactive (IR) nerve fibers were found in all layers of the alimentary tract and their distribution pattern was similar in both control and diabetic groups. Mast cell-nerve fiber contacts were rarely found in the controls. However, after 4 weeks duration of diabetes the number of IR nerve fibers and the immunocompetent cells increased significantly (P < 0.05), and the number of mast cell-nerve fiber contacts was even more significantly increased (P < 0.001). The distance between nerve fibers and immunocells was about 1 mum or even less. Some of the mast cells were degranulated in the vicinity of nerve fibers. No immunocompetent cells were IR for any antisera in the control. However, after the streptozotocin treatment, a large number of the immunocompetent cells showed immunoreactivity for SP and NPY. Counting all immunocompetent cells in whole sections showed that 12.3% of them were IR for SP and 25.4% were IR for NPY. Increased number of SP-containing nerve fibers and immunocells in diabetes mellitus might be the reason for painful neuropathy and might amplify the inflammatory reaction in an axon reflex manner; the released histamine and leukotrienes, cytokines, and chemokines might cause inflammations and lesions of the mucosa.

High-fat diet ingestion correlates with neuropathy in the duodenum myenteric plexus of obese mice with symptoms of type 2 diabetes

“…Substance P has also shown variable results in diabetic animal models. In streptozotocin-induced rats, the number of duodenal substance P reactive nerve fibers increased after 4 weeks (Feher et al 2006), while a study of longer duration (10 weeks) showed a reduction of substance P total content in stomach and small intestine (Ballman and Conlon 1985). Interestingly, a study looking at the small intestine and stomach during prolonged (12–18 month) streptozotocin-induced diabetes showed no change in substance P innervation between diabetic and control rats (Schmidt et al 1988).…”

Diabetes and the enteric nervous system

“…NPY, another inhibitory neurotransmitter, present predominantly in NANC neurons, often co‐localizes with nNOS 26 . Increase in NPY immunoreactivity in duodenum, colon and ileum has been reported in rats 25,27 . Obese diabetic mice also show increased NPY in the colon 28 .…”

“…Decrease in SP in stomach and ileum of rats at varied durations of 5–44 weeks of diabetes has also been reported. Although some studies demonstrate an increase in SP, 18,27 a majority of studies support a reduction in SP in diabetes 37,38 . Recent findings indicate that autoimmune attack on β‐cells as in diabetes type I appears to be triggered by abnormal sensory nerves that lack SP 39 .…”

“…26 Increase in NPY immunoreactivity in duodenum, colon and ileum has been reported in rats. 25,27 Obese diabetic mice also show increased NPY in the colon. 28 The concentration of galanin, another inhibitory peptide, was reduced in the colon of obese diabetic mice.…”

Neuropeptid Y és P anyag immunreaktív idegrostok és immunkompetens sejtek változása hepatitisben

“…Ezáltal befolyá-solja a különböző immunsejtek válaszát, például lymphocyták proliferációját, az NK-sejtek citotoxicitását, a különböző citokinek és antitestek termelését [1,2]. Az idegrostok mennyisége is megváltozik különböző gyulladásos folyamatokban és autoimmun betegségekben [3,4]. A legutóbbi irodalmi adatok számos zsigerben igazolták a neuropeptid IR idegrostok és immunkompetens sejtek szoros kapcsolatát, ami az ideg-és immunrendszer között meglévő kölcsönös egymásra hatás morfológiai bizonyítéka.…”