Epimedium flavonoids protect neurons and synapses in the brain via activating NRG1/ErbB4 and BDNF/Fyn signaling pathways in a chronic cerebral hypoperfusion rat model
Epimedium flavonoids protect neurons and synapses in the brain via activating NRG1/ErbB4 and BDNF/Fyn signaling pathways in a chronic cerebral hypoperfusion rat model
复制标题
淫羊藿黄酮类化合物通过激活慢性脑低灌注大鼠模型中的 NRG1/ErbB4 和 BDNF/Fyn 信号通路来保护大脑中的神经元和突触
DOI：
10.1016/j.brainresbull.2020.06.012
复制
发表时间：
2020-09-01
影响因子：
3.8
通讯作者：
Li, Lin
中科院分区：
文献类型：
--
作者：
Niu, Hong-Mei;Ma, Deng-Lei;Li, Lin
脑低灌注是脑小血管病（CSVD）的共同特征，近年来被认为是认知功能下降的原因之一。淫羊藿黄酮是从淫羊藿中提取的主要成分。本研究旨在探讨EF对双侧颈总动脉（2 VO）永久性闭塞大鼠认知功能障碍的影响及其机制。从2 VO手术后2周开始，灌胃给予EF（50、100和200 mg/kg）12周。结果表明，EF治疗改善了2 VO大鼠的学习和记忆障碍，通过新物体识别和Y-迷宫测试评估。NeuN免疫组织化学染色显示EF可减轻2 VO大鼠海马和大脑皮质神经元的丢失。MAP-2免疫荧光染色和Western blotting结果显示，EF对2 VO大鼠海马神经元树突有保护作用，并增加了细胞骨架蛋白MAP-2和NF-200的表达。透射电镜观察，EF对2 VO大鼠海马突触超微结构有保护作用，并增加突触可塑性相关蛋白synaptophysin、synaptotagmin-I、synapsin I、PSD-95、p-NMDA 2B、p-CaMK Ⅱ-α的表达。此外，EF还可增加2 VO大鼠海马神经调节蛋白1（NRG-1）、p-ErbB 4、脑源性神经营养因子（BDNF）、p-Fyn、PI 3 K、p-Akt和p-CREB的表达。提示EF可能通过激活海马和大脑皮层的NRG 1/ErbB 4、BDNF/Fyn和P13 K/Akt/CREB通路保护神经元和突触，从而改善慢性脑低灌注所致的认知功能障碍。EF可能是治疗慢性脑低灌注和CSVD的潜在候选药物。
Cerebral hypoperfusion is a common feature of cerebral small vascular disease (CSVD), which has been considered as one of the causes of cognitive decline in recent years. Epimedium flavonoids (EF) are the main ingredients extracted from Epimedium. The purpose of this study was to investigate the effects of EF on cognitive impairment, and the underlying mechanisms in rats with permanent occlusion of the bilateral common carotid artery (2VO). EF (50, 100, and 200 mg/kg) was intragastrically administered for 12 weeks starting 2 weeks after 2VO surgery. The results showed that EF treatment improved learning and memory impairment in 2VO rats evaluated by novel object recognition and Y-maze tests. NeuN immunohistochemical staining indicated that EF alleviated neuronal loss in the hippocampus and cerebral cortex of 2VO rats. MAP-2 immunofluorescence staining and western blotting showed that EF protected neuronal dendrites and increased the expression of cytoskeleton proteins MAP-2 and NF200 in the hippocampus of 2VO rats. Moreover, EF protected the synapse ultrastructure detected by transmission electron microscopy, and increased the expression of synaptic plasticity-related proteins, including synaptophysin, synaptotagmin-I, synapsin I, PSD-95, p-NMDA2B, and p-CaMKII-alpha in the hippocampus of 2VO rats. In addition, EF increased the expression of neuregulin-1 (NRG-1), p-ErbB4, brain-derived neurotrophic factor (BDNF), p-Fyn, PI3K, p-Akt, and p-CREB in the hippocampus of 2VO rats. These results suggest that EF may protect neurons and synapses by activating the NRG1/ErbB4, BDNF/Fyn, and P13 K/Akt/CREB pathways in the hippocampus and cerebral cortex, thus improving cognitive impairment induced by chronic cerebral hypoperfusion. EF may be a potential candidate drug for chronic cerebral hypoperfusion and CSVD therapy.