Enteric Glial Network in Diabetes: Quantitative Changes of Glial Density in Rats in Response to Acute and Chronic...

Background/Objectives: Enteric glial cells (EGCs) are key players in regulating enteric neurons and gastrointestinal functions including disturbed gut motility in diabetic patients. Enteric neuronal damage has been shown in type 1 diabetes, but EGCs' vulnerability to hyperglycaemic insults requires more investigation. Therefore, we aimed to study the quantitative changes in the EGC network enmeshing enteric plexuses, intestinal smooth muscle and mucosa in streptozotocin-induced acute (1-week) and chronic (10-weeks) diabetic rat models. Methods: Fluorescent immunohistochemistry using Sox10 glial and HuC/HuD pan-neuronal markers, immunogold electron microscopy and ELISA were performed on different gut segments. Results: In the submucosal ganglia of the ileum and colon, the density of Sox10-immunoreactive EGCs was significantly reduced in acute and increased in chronic hyperglycaemic rats without any changes in the duodenum. In the myenteric ganglia, regionally distinct alterations of glial density were noted in acute hyperglycaemia; however, a remarkable decrease was observed in chronic animals. Alterations of neuronal density did not follow the pattern of glial changes, resulting in shifts in the glia/neuron ratio. The presence of Sox10-HuC/HuD-immunoreactive cells and their diabetes-related quantitative changes were also revealed in enteric plexuses. The density of Sox10-labelling gold particles was significantly increased in the duodenal myenteric glia of diabetic rats. Muscular EGC density increased only in the colon after acute hyperglycaemia and changed in all segments after chronic hyperglycaemia. Glial fibrillary acidic protein levels decreased in the small intestine of chronic hyperglycaemic rats. Conclusions: Our present findings reveal time-dependent and regionally distinct changes in the EGC network in response to hyperglycaemia, contributing to diabetic enteric neuropathy and gut motility disturbances.