School of Life Sciences, Lanzhou University, Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou 730000, Gansu Province, PR China.
School of Life Sciences, Northwest Normal University, Lanzhou 730070, Gansu Province, PR China.
Phytomedicine. 2024 Sep;132:155803. doi: 10.1016/j.phymed.2024.155803. Epub 2024 Jun 8.
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.
This study investigated whether AS-IV could play a neuroprotective role by regulating BDNF-TrkB pathway in radiation damage and its underlying molecular mechanisms.
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 μg/ml and 50 μg/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.
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.
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.
电磁辐射与人类生活息息相关，辐射通过氧化应激、线粒体功能障碍和蛋白质降解等方式改变中枢神经系统的功能，从而引发神经退行性疾病。黄芪甲苷（AS-IV）具有抗氧化、抗凋亡作用，可激活 BDNF-TrkB 通路，增强辐射小鼠的突触可塑性，发挥其神经保护作用。但是，确切的分子机制尚不清楚。
本研究旨在探讨 AS-IV 是否通过调节 BDNF-TrkB 通路在辐射损伤中发挥神经保护作用及其潜在的分子机制。
通过腹腔注射给予转基因小鼠（Thy1-YFP 线 H）AS-IV（40mg/kg/天体重），每天 1 次，连续 4 周，然后进行 X 射线照射。体外培养 PC12 细胞和原代皮质神经元，用 AS-IV（25μg/ml 和 50μg/ml）预处理 24 小时后，用 UVA 照射。在 Morris 水迷宫实验中观察辐射对学习和认知功能的影响。随后，采用免疫荧光和高尔基染色分析观察神经元树突的结构损伤和树突棘密度。透射电镜观察辐射对神经元超微结构的影响。最后，采用 Western blot 分析和定量 RT-PCR 检测体外和体内蛋白质的表达水平和位置。
辐射诱导 BDNF-TrkB 信号通路失调，降低神经元相关功能基因（Ngf、Bdnf、Gap-43、Ras、Psd-95、Arc、Creb、c-Fos）、PSD-95 和 F-actin 的水平，导致神经元超微结构和树突损伤，树突棘丢失，树突复杂性指数降低，从而导致空间学习和记忆缺陷。AS-IV 治疗可预防这些异常。此外，TrkB 受体拮抗剂拮抗 AS-IV 的这些神经保护作用。7,8-二羟基黄酮和 AS-IV 在辐射后具有神经保护作用。
AS-IV 抑制辐射暴露后小鼠神经元形态损伤和认知功能障碍，发挥神经保护作用，其机制与激活 BDNF-TrkB 通路有关。
