• Yan Chen, Shuhui Zhang, Ying Li, Hui Yan, Ying Ba, Xuemin Wang, Ning Shi, and Chengxia Liu.
• Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, China.
• Neuromodulation. 2022 Dec 1; 25 (8): 110611141106-1114.

BackgroundLack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. This study aimed to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved.Materials And MethodsA total of 60 rats were randomized into six groups, including the normal control group, diabetic group (DM), diabetic with sham GES group (DM + SGES), and three groups of diabetic rats with GES (DM + GES1, DM + GES2, and DM + GES3). The proliferation of ICC and expressions of 5-hydroxytryptamine (serotonin) receptor 2B (5-HT2B), neuronal nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5, and glia cell line-derived neurotrophic factor (GDNF) in the antrum of the stomach were evaluated by immunofluorescence staining or Western blot. The levels of 5-HT in blood and tissue were determined by enzyme-linked immunosorbent assay.ResultsThe proliferation of ICC was significantly reduced in the DM group, together with the DM + SGES group, but increased in the three DM + GES groups. The expression of 5-HT2B was decreased in the DM group and enhanced in the DM + GES groups. Similarly, the levels of 5-HT in the blood and distal stomach tissue were increased in the DM + GES groups. Both nNOS labeled neurons and CHAT-positive neurons were reduced in the myenteric plexus of the DM group, whereas these neurons were dramatically increased the in DM + GES groups. The expression of GDNF protein in the diabetic rats was down-regulated, whereas GES increased the expression of GDNF.ConclusionsGES improves the proliferation of ICC possibly related with the 5-HT/5-HT2B signal pathway and alters the enteric nervous system partly though the GDNF expression.Copyright © 2021. Published by Elsevier Inc.

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