Estrogen deficiency exacerbates learning and memory deficits associated with glucose metabolism disorder in APP/PS1 double female mice

作者全名："Luo, Min; Zeng, Qinghua; Jiang, Kai; Zhao, Yueyang; Long, Zhimin; Du, Yexiang; Wang, Kejian; He, Guiqiong"

作者地址："[Luo, Min; Zeng, Qinghua; Zhao, Yueyang; Long, Zhimin; Du, Yexiang; Wang, Kejian; He, Guiqiong] Chongqing Med Univ, Chongqing Key Lab Neurobiol, Chongqing 400016, Peoples R China; [Luo, Min] TCM, Dept Pathol, Suining Municipal Hosp, Suining 629000, Sichuan, Peoples R China; [Zeng, Qinghua; Long, Zhimin; Wang, Kejian; He, Guiqiong] Chongqing Med Univ, Dept Anat, Chongqing 400016, Peoples R China; [Jiang, Kai] Suining Cent Hosp, Dept Gastroenterol, Suining 629000, Sichuan, Peoples R China; [He, Guiqiong] Chongqing Med Univ, Chongqing Key Lab Neurobiol, 1 YiXueYuan Rd, Chongqing 400016, Peoples R China"

通信作者："Wang, KJ; He, GQ (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Neurobiol, Chongqing 400016, Peoples R China.; Wang, KJ; He, GQ (通讯作者)，Chongqing Med Univ, Dept Anat, Chongqing 400016, Peoples R China.; He, GQ (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Neurobiol, 1 YiXueYuan Rd, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000831198700020

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：9

期号：5

开始页：1315

结束页：1331

文献类型：Article

关键词：Alzheimer?s disease; Estrogen deficiency; Glucose metabolism disorder; GSK-3b; IGF-1; Mitochondria

摘要："Alterations in glucose metabolism occur in the brain in the early stage of Alzhei-mer's disease (AD), and menopausal women have more severe metabolic dysfunction and are more prone to dementia than men. Although estrogen deficiency-induced changes in glucose metabolism have been previously studied in animal models, their molecular mecha-nisms in AD remain elusive. To investigate this issue, double transgenic (APP/PS1) female mice were subjected to bilateral ovariectomy at 3 months of age and were sacrificed 1 week, 1 month and 3 months after surgery to simulate early, middle and late postmenopause, respec-tively. Our analysis demonstrated that estrogen deficiency exacerbates learning and memory deficits in this mouse model of postmenopause. Estrogen deficiency impairs the function of mitochondria in glucose metabolism. It is possible that the occurrence of AD is associated with the aberrant mitochondrial ERI3-mediated IGF-1/IGF-1R/GSK-3 I3 signaling pathway. In this study, we established a potential mechanism for the increased risk of AD in postmenopausal women and proposed a therapeutic target for AD due to postmenopause.Copyright 2022, Chongqing Medical University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/)."

基金机构："National Natural Science Foundation of China [81671257, 81371221, 31600825]; Innovation Research Group at Institutions of Higher Education in Chongqing [CXQTP19019019034]"

基金资助正文："Funding This study was supported by the National Natural Science Foundation of China (No. 81671257, 81371221, and 31600825) and the Innovation Research Group at Institutions of Higher Education in Chongqing (No. CXQTP19019019034) ."