Remodeling of ammon's horn during the first two weeks of experimental diabetes development

It is known that long-term diabetes mellitus causes hippocampal dysfunction, however, early events leading to diabetes-related impairments of hippocampal tissue remain obscure. The present study was performed to examine temporal and spatial patterns of neuronal damage and astrogliosis in hippocampal CA1-C3 areas during the early stage of streptozotocin-induced diabetes in rats. NeuN and GFAP immunohistochemistry was used to visualize neurons and glial cells. Immunopositive cells were counted in hippocampal CA1-CA3 areas at days 3, 7 and 14 of diabetes development using confocal Olympus FV1000 microscope. Significant decrease in the number of neurons in CA2 area was observed in diabetic rats at day 3. In contrast, in CA1 and CA3 areas NeuN-positive cell count started to decrease later being at day 7, correspondingly, by 7 and 9 % lower than that in the control. This trend developed further till day 14, when the number of neurons in CA1 and CA3 areas was, respectively, 20.3 and 18.1% smaller as compared with the control. These changes were accompanied by astrogliosis: the number of astrocytes in pyramidal cell layer was increased significantly in all examined time-points. Thus, our study demonstrates that streptozotocin-induced diabetes is associated with early neurodegeneration in Ammon's horn. It suggests that clinically relevant cognitive deficits development in diabetic patients starting from the early stage of the disease.