Apicidin attenuates memory deficits by reducing the A beta load in APP/PS1 mice

作者全名："Luo, Biao; Chen, Jian; Zhou, Gui-Feng; Xie, Xiao-Yong; Tang, Jing; Wen, Qi-Xin; Song, Li; Xie, Shi-Qi; Long, Yan; Chen, Guo-Jun; Hu, Xiao-Tong"

作者地址："[Luo, Biao; Chen, Jian; Zhou, Gui-Feng; Xie, Xiao-Yong; Tang, Jing; Wen, Qi-Xin; Song, Li; Xie, Shi-Qi; Chen, Guo-Jun] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, Chongqing, Peoples R China; [Long, Yan; Hu, Xiao-Tong] Army Med Univ, Daping Hosp, Dept Hlth Management, Chongqing, Peoples R China; [Hu, Xiao-Tong] Ninth Peoples Hosp Chongqing, Dept Neurol, Chongqing, Peoples R China; [Hu, Xiao-Tong] Ninth Peoples Hosp Chongqing, Dept Neurol, Chongqing, Peoples R China; [Chen, Guo-Jun] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol,Affiliated Hosp 1, China, Chongqing, Peoples R China"

通信作者："Hu, XT (通讯作者)，Ninth Peoples Hosp Chongqing, Dept Neurol, Chongqing, Peoples R China.; Chen, GJ (通讯作者)，Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol,Affiliated Hosp 1, China, Chongqing, Peoples R China."

来源：CNS NEUROSCIENCE & THERAPEUTICS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000921274500001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：29

期号：5

开始页：1300

结束页：1311

文献类型：Article

关键词：ADAM10; Alzheimer's disease; apicidin; histone deacetylase inhibitor; phosphorylation tau

摘要："AimsAmyloid beta (A beta) is an important pathological feature of Alzheimer's disease (AD). A disintegrin and metalloproteinase 10 (ADAM10) can reduce the production of toxic A beta by activating the nonamyloidogenic pathway of amyloid precursor protein (APP). We previously found that apicidin, which is a histone deacetylase (HDAC) inhibitor, can promote the expression of ADAM10 and reduce the production of A beta in vitro. This study was designed to determine the potential of apicidin treatment to reverse learning and memory impairments in an AD mouse model and the possible correlation of these effects with ADAM10. MethodsNine-month-old APP/PS1 mice and C57 mice received intraperitoneal injections of apicidin or vehicle for 2 months. At 11 months of age, we evaluated the memory performance of mice with Morris water maze (MWM) and context fear conditioning tests. The A beta levels were assessed in mouse brain using the immunohistochemical method and ELISA. The expression of corresponding protein involved in proteolytic processing of APP and the phosphorylation of tau were assessed by Western blotting. ResultsApicidin reversed the deficits of spatial reference memory and contextual fear memory, attenuated the formation of A beta-enriched plaques, and decreased the levels of soluble and insoluble A beta 40/42 in APP/PS1 mice. Moreover, apicidin significantly increased the expression of ADAM10, improved the level of sAPP alpha, and reduced the production of sAPP beta, but did not affect the levels of phosphorylated tau in APP/PS1 mice. ConclusionApicidin significantly improves the AD symptoms of APP/PS1 mice by regulating the expression of ADAM10, which may contribute to decreasing the levels of A beta rather than decreasing the phosphorylation of tau."

基金机构：Chongqing Education commission [KJZD-K201900404]; National Natural Science Foundation of China [81971030]; Natural Science Foundation of Chongqing [cstc2019jcyj-msxmX0650]

基金资助正文："Chongqing Education commission, Grant/Award Number: KJZD-K201900404; National Natural Science Foundation of China, Grant/Award Number: 81971030; Natural Science Foundation of Chongqing, Grant/Award Number: cstc2019jcyj-msxmX0650"