机构：[1]Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.首都医科大学宣武医院[2]Department of Endocrinology, The Affiliated Huai'an First People's Hospital of Nanjing Medical University, Huai'an, China.[3]Department of Rehabilitation Medicine, Affiliated 3201 Hospital of Xi'an Jiaotong University School of Medicine, Hanzhong, China.[4]Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.[5]Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.[6]Department of Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.[7]Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA.
Cognitive impairment is closely associated with the slowing of glucose metabolism in the brain. Glucose transport, a rate-limiting step of glucose metabolism, plays a key role in this phenomenon. Previous studies have reported that limb remote ischemic conditioning (LRIC) improves cognitive performance in rats with chronic cerebral hypoperfusion (CCH). Here, we determined whether LRIC could ameliorate cognitive impairment in rats with CCH by regulating glucose transport. A total of 170 male Sprague-Dawley rats were used. Animals subjected to permanent double carotid artery occlusion (2VO) were assigned to the control or LRIC treatment group. LRIC was applied beginning 3 days after the 2VO surgery. We found that LRIC can improve learning and memory; decrease the ratio of ADP/ATP; increase glucose content; upregulate the expression of pAMPK alpha, GLUT1 and GLUT3; and increase the number of GLUT1 and GLUT3 transporters in cerebral cortical neurons. The expression of GLUT1 and GLUT3 in the cortex displayed a strong correlation with learning and memory. Pearson correlation analysis showed that the levels of GLUT1 and GLUT3 are correlated with neurological function scores. All of these beneficial effects of LRIC were ablated by application of the AMPK inhibitor, dorsomorphin. In summary, LRIC ameliorated cognitive impairment in rats with CCH by regulating glucose transport via the AMPK/GLUT signaling pathway. We conclude that AMPK-mediated glucose transport plays a key role in LRIC. These data also suggest that supplemental activation of glucose transport after CCH may provide a clinically applicable intervention for improving cognitive impairment.
基金：
This work was supported by the Natural Science Foundation of Beijing, China (7161014). National Natural Science Foundation of China (81971114, 81801313, 81573867), the Beijing Municipal Administration of Hospitals’ Youth Program (QML 20180801), the Science and Technology Development Project of the Beijing Municipal Health Commission and the National Key R&D Program of China (2017YFC1308402).
第一作者机构：[1]Beijing Key Laboratory of Hypoxia Translational Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.[5]Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.
共同第一作者：
通讯作者：
通讯机构：[5]Beijing Institute of Brain Disorders, Capital Medical University, Beijing, China.[*1]Beijing Institute of Brain Disorders, Capital Medical University, Beijing 100053, China.
推荐引用方式(GB/T 7714)：
Changhong Ren,Yuanyuan Liu,Christopher Stone,et al.Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport[J].AGING AND DISEASE.2021,12(5):1197-1210.doi:10.14336/AD.2020.1125.
APA：
Changhong Ren,Yuanyuan Liu,Christopher Stone,Ning Li,Sijie Li...&Yuchuan Ding.(2021).Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport.AGING AND DISEASE,12,(5)
MLA：
Changhong Ren,et al."Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport".AGING AND DISEASE 12..5(2021):1197-1210
