• Z-F Zuo, W Wang, L Niu, Z-Z Kou, C Zhu, X-H Zhao, D-S Luo, T Zhang, F-X Zhang, X-Z Liu, S-X Wu, and Y-Q Li.
• Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Center, Fourth Military Medical University, No. 169 West Changle Road, Xi'an 710032, PR China.
• Neuroscience. 2011 Sep 8; 190: 156-65.

AbstractDiabetic 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) participated in DCD. In the present study, three months after streptozotocin (STZ)-induced type-1 diabetes onset, rats showed 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.Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

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