Hippocampal heat shock protein 25 expression in streptozotocin-induced diabetic mice

Hippocampal abnormalities are believed to increase the risk of cognitive decline in diabetic patients. The underlying mechanism is unknown, but both hyperglycemia and oxidative stress have been implicated. Cellular stresses induce the expression of heat shock protein 25 (HSP25) and this results in cytoprotection. Our aim was to assess hippocampal expression of HSP25 in experimental diabetes. Mice were rendered diabetic by streptozotocin injection. Ten weeks after diabetes onset hippocampal HSP25 expression was studied by immunoblotting and immunohistochemistry (IHC). Expression of glial fibrillary acidic protein, nitrotyrosine, iNOS, HSP72, HSP90, and Cu/Zn superoxide dismutase (SOD) was assessed by either IHC or immunoblotting, Cu/Zn-SOD activity by enzymatic assay, and malondialdehyde (MDA) content by colorimetric assay. Hippocampal HSP25 was significantly increased in diabetic as compared to non-diabetic animals and localized predominantly within the pyramidal neurons layer of the CA1 area. This was paralleled by overexpression of nitrotyrosine, iNOS, SOD expression/activity, and enhanced MDA content. In experimental diabetes, HSP25 is overexpressed in the CA1 pyramidal neurons in parallel with markers of oxidative stress.

► The study was performed on streptozotocin-induced diabetic mice. ► HSP25 was overexpressed in the pyramidal CA1 layer of the diabetic hippocampus. ► Markers of oxidative stress were enhanced in the diabetic hippocampus. ► HSP25 upregulation may represent a protective mechanism against oxidative stress.