Early molecular events in the hippocampus of rats with streptozotocin-induced diabetes

In our study, we tried to find whether changes in expressions of inducible nitric oxide synthase (iNOS), corticosteroid (gluco-and mineralocorticoid) receptors (GRs and MRs, respectively), and bcl₂ protein within the early stages of streptozotocin (STZ)-induced diabetes in Wistar rats can be involved in hippocampal dysfunction. Expressions of iNOS and bcl₂ were studied using indirect immunofluorescence techniques, while GR and MR expressions were estimated using in situ mRNA hybridization. The concentrations of insulin, ACTH, and corticosterone in the blood serum were measured using ELISA kits. It was found that expression of iNOS in the CA2 and CA3 hippocampal areas increased significantly at day 3 after STZ injection, and corticosterone and ACTH levels in the serum increased at day 14. The iNOS expression was downregulated at day 14 of the development of diabetes. These changes were accompanied by significantly increased expression of GRs in the hippocampus. Neither bcl₂ nor MR expression increased in the CA2 and CA3 hippocampal areas within the examined period of the development of diabetes. Thus, we first obtained proof of noticeable early molecular events in the rat hippocampus related to experimental diabetes. These events may be linked with diabetes-associated cognitive decline observed in patients suffering from diabetes. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 498–502, November–December, 2007.