Effects of Acute and Chronic Hyperglycemia on Neurotrophic Factors in the Gut: GDNF and NT3 Expression in Myenteric Ganglia

Background/Objectives: Glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT3) are essential neurotrophic factors that continue to be expressed in the mature intestine. Myenteric neurons are damaged by hyperglycemia to varying degrees in the different gut segments. Therefore, our aims were to identify the gut-segment-specific expression patterns of GDNF and NT3 in acute and chronic hyperglycemic rat models. Methods: Segments of the duodenum, ileum, and colon were dissected one week (acute experiment) or ten weeks (chronic experiment) after the streptozotocin-induced hyperglycemia. GDNF–HuC/HuD fluorescent immunohistochemistry, NT3 enzyme-linked immunosorbent assay, and NT3 immunogold electron microscopy were performed in rat myenteric ganglia. Results: The proportion of GDNF–immunoreactive myenteric neurons did not change in gut segments in acute hyperglycemia. However, during chronic diabetes, it was elevated in the colon and remained unchanged in the duodenum and ileum. Expressional alterations of NT3 were investigated in the small intestine. In duodenal myenteric ganglia, acute hyperglycemia induced a significant increase in the number of NT3-labeling gold particles, and its density was markedly increased in chronic diabetes, which was partially prevented by insulin treatment. In the ileum, NT3 density increased in acute hyperglycemic rats, while it decreased in chronic diabetic rats. Conclusions: Induction of neurotrophic factors was specific to different gut segments during acute and chronic hyperglycemia. These results suggest that increased colonic GDNF and duodenal NT3 expression may reflect a compensatory response of myenteric neurons to hyperglycemic states.