Octadecaneuropeptide Ameliorates Cognitive Impairments Through Inhibiting Oxidative Stress in Alzheimer's Disease Models

作者全名："He, Yan; Li, Junjie; Yi, Liling; Li, Xiaohuan; Luo, Man; Pang, Yayan; Wang, Maoju; Li, Zhaolun; Xu, Mingliang; Dong, Zhifang; Du, Yehong"

作者地址："[He, Yan; Li, Junjie; Yi, Liling; Li, Xiaohuan; Luo, Man; Pang, Yayan; Wang, Maoju; Li, Zhaolun; Xu, Mingliang; Dong, Zhifang; Du, Yehong] Chongqing Med Univ, Pediat Res Inst,Minist Educ,Key Lab Child Dev & D, Childrens Hosp,Chongqing Key Lab Translat Med Res, Natl Clin Res Ctr Child Hlth & Disorders,China In, Chongqing 400014, Peoples R China"

通信作者："Dong, ZF; Du, YH (通讯作者)，Chongqing Med Univ, Pediat Res Inst,Minist Educ,Key Lab Child Dev & D, Childrens Hosp,Chongqing Key Lab Translat Med Res, Natl Clin Res Ctr Child Hlth & Disorders,China In, Chongqing 400014, Peoples R China."

来源：JOURNAL OF ALZHEIMERS DISEASE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000971602900020

JCR分区：Q2

影响因子：3.4

年份：2023

卷号：92

期号：4

开始页：1413

结束页：1426

文献类型：Article

关键词：Alzheimer's disease; amyloid-beta; cognition; octadecaneuropeptide; oxidative stress

摘要："Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta peptide (A beta) deposition. A beta accumulation induces oxidative stress, leading to mitochondrial dysfunction, apoptosis, and so forth. Octadecaneuropeptide (ODN), a diazepam-binding inhibitor (DBI)-derived peptide, has been reported to have antioxidant properties. However, it is unclear whether ODN has neuroprotective effects in AD. Objective: To profile the potential effects of ODN on AD. Methods: We established a mouse model of AD via microinjection of A beta in the lateral ventricle. Utilizing a combination of western blotting assays, electrophysiological recordings, and behavioral tests, we investigated the neuroprotective effects of ODN on AD. Results: DBI expression was decreased in AD model mice and cells. Meanwhile, ODN decreased A beta generation by downregulating amyloidogenic A beta PP processing in HEK-293 cells stably expressing human Swedish mutant APP695 and BACE1 (2EB2). Moreover, ODN could inhibit A beta-induced oxidative stress in primary cultured cells and mice, as reflected by a dramatic increase in antioxidants and a decrease in pro-oxidants. We also found that ODN could reduce oxidative stress-induced apoptosis by restoring mitochondrial membrane potential, intracellular Ca2+ and cleaved caspase-3 levels in A beta-treated primary cultured cells and mice. More importantly, intracerebroventricular injection of ODN attenuated cognitive impairments as well as long-term potentiation in A beta-treated mice. Conclusion: These results suggest that ODN may exert a potent neuroprotective effect against A beta-induced neurotoxicity and memory decline via its antioxidant effects, indicating that ODN may be a potential therapeutic agent for AD."

基金机构："National Natural Science Foundation of China [82071395, 82001158]; Natural Science Foundation of Chongqing [cstc2020jcyj-zdxmX0004, cstc2021ycjh-bgzxm0186, 2022NSCQ-LZX0018]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K201900403]; Innovation Research Group at Institutions of Higher Education in Chongqing [CXQTP19034]; CQMU Program for Youth Innovation in Future Medicine [W0044]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (82071395 and 82001158), the Natural Science Foundation of Chongqing (cstc2020jcyj-zdxmX0004, cstc2021ycjh-bgzxm0186 and 2022NSCQ-LZX0018), the Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-K201900403), Innovation Research Group at Institutions of Higher Education in Chongqing (CXQTP19034), CQMU Program for Youth Innovation in Future Medicine (W0044)."