Diabetic cognitive dysfunction(DCD),usually accompanied with chronically elevated glucocorticoids and hippocampal astrocytic alterations,is one of the most serious complications in patients with type 1 diabetes.However,the role for chronically elevated glucocorticoids and hippocampal astrocytic activations in DCD remains to be elucidated,and it is not clear whether astrocytic N-myc downstream-regulated gene 2(NDRG2,involved in cell differentiation and development)is participated in DCD.In the present study,three months after streptozotocin(STZ)-induced type 1 diabetes onset,rats showed significant cognitive impairments in Morris water maze test as well as elevated corticosterone level.Diabetic rats also presented down-regulation of glial fibrillary acidic protein(GFAP,a key indicator of astrocytic reactivity)and NDRG2 in hippocampus revealed by immunohistochemistry staining,real-time PCR and Western blot.Moreover,the diabetic cognitive impairments were ameliorated by 9-day glucocorticoids receptor(GR)blockade with RU486,and the down-regulation of hippocampal NDRG2 and GFAP in diabetic animals was also attenuated by 9-day GR blockade.These results suggest that glucocorticoids-GR system is crucial for DCD,and that astrocytic reactivity and NDRG2 are involved in these processes.Thus,inhibiting GR activation in the hippocampus may be a novel therapeutic strategy for treating DCD.