Rosiglitazone attenuates cognitive function via altering hippocampal IRS-1/Akt signaling pathways in ob/ob mouse
10.3969/j.issn.1001-1978.2015.06.010
- VernacularTitle:罗格列酮通过IRS-1/Akt信号通路改善ob/ob小鼠的认知功能障碍
- Author:
Shuiqin CHAI
;
Jibin LI
;
Hongying WANG
;
Ye SONG
;
Dan LIU
;
Xiaoqiu XIAO
- Publication Type:Journal Article
- Keywords:
rosiglitazone;
ob/ob mice;
insulin resist-ance;
IRS1/Akt;
BACE1;
cognitive dysfunction
- From:
Chinese Pharmacological Bulletin
2015;(6):785-789
- CountryChina
- Language:Chinese
-
Abstract:
Aim To identify alteration in key molecular components related to memory formation and insulin signaling in the hippocampus after rosiglitazone was in-jected into the ob/ob mice to test whether cognitive dysfunction was pharmacologically reversed by regula-tion of rosiglitazone. Methods The age-matched mice were divided into three groups ( n=18 ): Saline-trea-ted WT mice ( WT-Saline);Saline-treated ob/ob mice ( ob/ob-Saline) and RSG-treated ob/ob mice ( ob/ob-RSG) through intraperitoneal injection of rosiglitazone ( RSG) . The random glucose levels were measured for 10 days during the intraperitoneal injection period. No-vel object recognition was performed before mice were sacrificed. Western blot was implemented to evaluate the following proteins: BACE1, p-Tau, p-IRS1,IRS1, p-Akt and Akt in hippocampal tissues. The Aβ1-40 levels were detected by ELISA Kit. Results The random blood glucose levels were significantly re-duced in ob/ob-RSG compared with ob/ob-saline. RSG treatment led to an increase in hippocampus-de-pendent cognition of ob/ob mice according to the novel object recognition. The proteins levels of BACE1, p-Tau and Aβ were lowered in RSG-treated ob/ob mice. Furthermore, RSG treatment up-regulated hippocampal p-IRS1/IRS1 and p-Akt/Akt ratio. Conclusion Ros-iglitazone ameliorates cognitive deficits in ob/ob mice through up-regulating insulin signaling pathways in the hippocampus.
