title: RU486 (mifepristone) ameliorates cognitive dysfunction and reverses the down-regulation of astrocytic N-myc downstream-regulated gene 2 in streptozotocin-induced type-1 diabetic rats.
abstract: 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) 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.
authors.affiliation: 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.
authors.forename: Z-F
authors.initials: ZF
authors.lastname: Zuo
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Niu
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Kou
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: X-H
authors.initials: XH
authors.lastname: Zhao
authors.forename: D-S
authors.initials: DS
authors.lastname: Luo
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: F-X
authors.initials: FX
authors.lastname: Zhang
authors.forename: X-Z
authors.initials: XZ
authors.lastname: Liu
authors.forename: S-X
authors.initials: SX
authors.lastname: Wu
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Li
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015735:Mifepristone / Q000494:pharmacology* / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: C507213:Ndrg2 protein, rat; D009419:Nerve Tissue Proteins; D015735:Mifepristone; D013311:Streptozocin; D003345:Corticosterone