The Protective Role of Caffeine against Histological and Ultrastructural Changes of Peripheral Nerve in Type 2 Diabetic Rats

Abstract: Type 2 diabetes mellitus (T2DM) is linked to injuries to many organs including the nervous system. Diabetic peripheral neuropathy (DPN) is a common complication of diabetes; it can result in disruption of Schwann cells (SCs) function, degeneration of nerve axons and demyelination. SCs provide trophic support to neurons and myelin formation and their role in nerve injury and regeneration is very crucial. Caffeine, a psychoactive beverage, was found to reduce the risk of many disorders including nervous system degeneration. The purpose of this study was to address the role of caffeine in peripheral nerve degeneration in a rat model of T2DM. Wistar rats were fed with a high caloric diet and injected with a single low dose of streptozotocin (STZ). Caffeine was administered to the rats orally for 5 weeks and was given one week before injection of STZ. The rats were sacrificed, then sciatic nerves were harvested, and processed for histological and electron microscopic evaluations. Immunohistochemistry was also done using the primary antibodies: anti S-100 (Schwann cell marker), anti-MBP (myelin basic protein) and anti-VEGF-A (vascular endothelial growth factor A). Examination of the sciatic nerve of diabetic rats revealed degeneration of SCs and axons, myelin, and connective tissue coverings. There was decrease in immunostaining of S-100 and MBP and increase in VEGFA, in diabetic rats. Administration of caffeine to diabetic rats resulted in improvement of histological and ultrastructural changes and upregulation of S-100, MBP, and downregulation of VEGFA. There were degenerative changes of the sciatic nerve of diabetic rats that were ameliorated by the administration of caffeine. © Pleiades Publishing, Ltd. 2024. ISSN 1990-519X, Cell and Tissue Biology, 2024, Vol. 18, No. 5, pp. 535–548. Pleiades Publishing, Ltd., 2024.