文献类型：期刊文献

英文题名：Astragaloside IV mediates radiation-induced neuronal damage through activation of BDNF-TrkB signaling

作者：Liu, Xin[1];Ding, Yanping[2];Jiang, Chenxin[1];Xin, Yuanyuan[1];Ma, Xin[1];Xu, Min[1];Wang, Qianhao[1];Hou, Boru[3];Li, Yingdong[4];Zhang, Shengxiang[1];Shao, Baoping[1]

第一作者：Liu, Xin

通信作者：Shao, BP[1]

机构：[1]Lanzhou Univ, Sch Life Sci, Key Lab Biomonitoring & Bioremediat Environm Pollu, Lanzhou 730000, Gansu, Peoples R China;[2]Northwest Normal Univ, Sch Life Sci, Lanzhou 730070, Gansu, Peoples R China;[3]Lanzhou Univ, Hosp 2, Dept Neurosurg, Lanzhou 730030, Gansu, Peoples R China;[4]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou 730000, Gansu, Peoples R China

第一机构：Lanzhou Univ, Sch Life Sci, Key Lab Biomonitoring & Bioremediat Environm Pollu, Lanzhou 730000, Gansu, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Sch Life Sci, Key Lab Biomonitoring & Bioremediat Environm Pollu, Lanzhou 730000, Gansu, Peoples R China.

年份：2024

卷号：132

外文期刊名：PHYTOMEDICINE

收录：;Scopus(收录号：2-s2.0-85195660575);WOS:【SCI-EXPANDED(收录号:WOS:001254146500001)】；

基金：This work was supported by the School of Life Sciences, Lanzhou University, Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Gansu Province (Gansu Province/Lanzhou University) . We thank Dr. S.Z. for sharing transgenic mice. This study was supported by the Natural Science Foundation of China (31760271 to Y.D.) , the Gansu Natural Science Foundation (23JRRA714 to Y.D.) , the Major Gansu Province Research Development Program (17YF1NA064 to B.S.) , the Major State Basic Research Development Program (2018YFC1706300 to B.S.) , the Institute of Neuroscience, Chinese Academy of Sciences Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences (SKLN2015B05 to B. S.) , and the Gansu Provincial Education Science and Technology Innovation Program (2021jyjbgs-03 to Y.L) . We would like to thank the Research and Experiment Center of School of Life Sciences in Lanzhou University.

语种：英文

外文关键词：Astragaloside IV; Radiation; Neuronal damage; BDNF-TrkB signaling pathway

摘要：Background: Electromagnetic radiation is relevant to human life, and radiation can trigger neurodegenerative diseases by altering the function of the central nervous system through oxidative stress, mitochondrial dysfunction, and protein degradation. Astragaloside IV (AS-IV) is anti-oxidative, anti-apoptotic, activates the BDNF-TrkB pathway and enhances synaptic plasticity in radiated mice, which can exert its neuroprotection. However, the exact molecular mechanisms are still unclear. Purpose: This study investigated whether AS-IV could play a neuroprotective role by regulating BDNF-TrkB pathway in radiation damage and its underlying molecular mechanisms. Methods: Transgenic mice (Thy1-YFP line H) were injected with AS-IV (40 mg/kg/day body weight) by intraperitoneal injection daily for 4 weeks, followed by X-rays. PC12 cells and primary cortical neurons were also exposed to UVA after 24 h of AS-IV treatment (25 mu g/ml and 50 mu g/ml) in vitro. The impact of radiation on learning and cognitive functions was visualized in the Morris water maze assay. Subsequently, Immunofluorescence and Golgi-Cox staining analyses were utilized to investigate the structural damage of neuronal dendrites and the density of dendritic spines. Transmission electron microscopy was performed to examine how the radiation affected the ultrastructure of neurons. Finally, western blotting analysis and Quantitative RT-PCR were used to evaluate the expression levels and locations of proteins in vitro and in vivo. Results: Radiation induced BDNF-TrkB signaling dysregulation and decreased the levels of neuron-related functional genes (Ngf, Bdnf, Gap-43, Ras, Psd-95, Arc, Creb, c-Fos), PSD-95 and F-actin, which subsequently led to damage of neuronal ultrastructure and dendrites, loss of dendritic spines, and decreased dendritic complexity index, contributing to spatial learning and memory deficits. These abnormalities were prevented by AS-IV treatment. In addition, TrkB receptor antagonists antagonized these neuroprotective actions of AS-IV. 7,8-dihydroxyflavone and AS-IV had neuroprotective effects after radiation. Conclusion: AS-IV inhibits morphological damage of neurons and cognitive dysfunction in mice after radiation exposure, resulting in a neuroprotective effect, which were mediated by activating the BDNF-TrkB pathway.