Dietary salt promotes cognition impairment through GLP-1R/mTOR/p70S6K signaling pathway

作者全名：Yang, Xu; Liu, Shu; Wang, Chuanling; Fan, Haixia; Zou, Qian; Pu, Yingshuang; Cai, Zhiyou

作者地址：[Yang, Xu; Cai, Zhiyou] Southwest Med Univ, Affiliated Hosp, Dept Neurol, Luzhou 646000, Sichuan, Peoples R China; [Yang, Xu; Liu, Shu; Wang, Chuanling; Fan, Haixia; Zou, Qian; Pu, Yingshuang; Cai, Zhiyou] Chongqing Univ, Chongqing Gen Hosp, Dept Neurol, 118 Xingguang Ave, Chongqing 401147, Peoples R China; [Yang, Xu; Liu, Shu; Wang, Chuanling; Fan, Haixia; Zou, Qian; Pu, Yingshuang; Cai, Zhiyou] Chongqing Key Lab Neurodegenerat Dis, Chongqing 312,Zhongshan First Rd, Chongqing 400013, Peoples R China; [Wang, Chuanling] Chongqing Med Univ, Sch Basic Med, Dept Pathophysiol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Cai, Zhiyou] Chongqing Gen Hosp, Dept Neurol, 312 Zhongshan First Rd, Chongqing 400013, Peoples R China

通信作者：Cai, ZY (通讯作者)，Southwest Med Univ, Affiliated Hosp, Dept Neurol, Luzhou 646000, Sichuan, Peoples R China.; Cai, ZY (通讯作者)，Chongqing Univ, Chongqing Gen Hosp, Dept Neurol, 118 Xingguang Ave, Chongqing 401147, Peoples R China.; Cai, ZY (通讯作者)，Chongqing Key Lab Neurodegenerat Dis, Chongqing 312,Zhongshan First Rd, Chongqing 400013, Peoples R China.; Cai, ZY (通讯作者)，Chongqing Gen Hosp, Dept Neurol, 312 Zhongshan First Rd, Chongqing 400013, Peoples R China.

来源：SCIENTIFIC REPORTS

ESI学科分类：Multidisciplinary

WOS号：WOS:001197575500034

JCR分区：Q1

影响因子：3.8

年份：2024

卷号：14

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Dietary salt; High-salt diet (HSD); Normal diet (ND); Cognition impairment; Tau hyperphosphorylation

摘要：Dietary salt has been associated with cognitive impairment in mice, possibly related to damaged synapses and tau hyperphosphorylation. However, the mechanism underlying how dietary salt causes cognitive dysfunction remains unclear. In our study, either a high-salt (8%) or normal diet (0.5%) was used to feed C57BL/6 mice for three months, and N2a cells were cultured in normal medium, NaCl medium (80 mM), or NaCl (80 mM) + Liraglutide (200 nM) medium for 48 h. Cognitive function in mice was assessed using the Morris water maze and shuttle box test, while anxiety was evaluated by the open field test (OPT). Western blotting (WB), immunofluorescence, and immunohistochemistry were utilized to assess the level of Glucagon-like Peptide-1 receptor (GLP-1R) and mTOR/p70S6K pathway. Electron microscope and western blotting were used to evaluate synapse function and tau phosphorylation. Our findings revealed that a high salt diet (HSD) reduced the level of synaptophysin (SYP) and postsynaptic density 95 (PSD95), resulting in significant synaptic damage. Additionally, hyperphosphorylation of tau at different sites was detected. The C57BL/6 mice showed significant impairment in learning and memory function compared to the control group, but HSD did not cause anxiety in the mice. In addition, the level of GLP-1R and autophagy flux decreased in the HSD group, while the level of mTOR/p70S6K was upregulated. Furthermore, liraglutide reversed the autophagy inhibition of N2a treated with NaCl. In summary, our study demonstrates that dietary salt inhibits the GLP-1R/mTOR/p70S6K pathway to inhibit autophagy and induces synaptic dysfunction and tau hyperphosphorylation, eventually impairing cognitive dysfunction.

基金机构：Chongqing Talent Project

基金资助正文：No Statement Available