Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and β-Amyloid Accumulation in an APP/tau/PS1 Mouse Model of Alzheimer's Disease.

Berberine Improves Cognitive Impairment by Simultaneously Impacting Cerebral Blood Flow and β-Amyloid Accumulation in an APP/tau/PS1 Mouse Model of Alzheimer's Disease.
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小檗碱通过同时影响阿尔茨海默病 APP/tau/PS1 小鼠模型的脑血流和 β-淀粉样蛋白积累来改善认知障碍

DOI:
10.3390/cells10051161
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发表时间:
2021-05-11
期刊:
影响因子:
6
通讯作者:
Huang M
Huang M
中科院分区:
生物学2区
文献类型:
--
作者:
Ye C;Liang Y;Chen Y;Xiong Y;She Y;Zhong X;Chen H;Huang M

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阿尔茨海默病(Alzheimer's disease,AD)是一种伴有β-淀粉样蛋白(β-amyloid,Aβ)、神经元缠结和神经元细胞死亡的老年性疾病。AD的病理学是复杂的,涉及Aβ过度产生和积累、tau过度磷酸化和神经元损失。此外,慢性脑灌注不足(CCH)在AD患者中普遍存在,并在触发和加重AD的病理生理进展中起关键作用。本研究旨在探讨小檗碱(BBR)的神经保护作用及其机制。在研究过程中,BBR被给予治疗阿尔茨海默病的三转基因小鼠模型(3×Tg AD)。采用三维动脉自旋标记技术、Morris水迷宫实验、免疫荧光染色、TUNEL法、激光散斑衬度成像、Western blotting等多种方法对BBR的作用进行了全面的评价。结果表明,BBR能改善3×Tg AD小鼠的认知功能障碍,减少Aβ积聚,抑制神经元凋亡,通过增强脑组织中CD 31、VEGF、N-cadherin、Ang-1的表达,促进小鼠脑微血管的形成。BBR促进的新生血管结构完整、功能完善,促进了脑血流量的恢复。总体而言,小檗碱对3×Tg AD小鼠有效,具有神经保护作用,是AD多靶点防治的候选药物。
Alzheimer’s disease (AD) is accompanied by β-amyloid (Aβ), neurofibrillary tangles, and neuron cell death, and is one of the most commonly occurring diseases among the elderly. The pathology of AD is complex, involving Aβ overproduction and accumulation, tau hyperphosphorylation, and neuronal loss. In addition, chronic cerebral hypoperfusion (CCH) is ubiquitous in the AD patients and plans a pivotal role in triggering and exacerbating the pathophysiological progress of AD. The goal of this study was to investigate the neuroprotective properties of berberine (BBR) and the underlying mechanism. During the study, BBR was administrated to treat the triple-transgenic mouse model of Alzheimer’s disease (3×Tg AD). To thoroughly evaluate the effects of the BBR administration, multiple manners were utilized, for instance, 3D arterial spin labeling technique, Morris water maze assay, immunofluorescence staining, TUNEL assay, laser speckle contrast imaging, western blotting, etc. The results showed that BBR ameliorated cognitive deficits in 3×Tg AD mice, reduced the Aβ accumulation, inhibited the apoptosis of neurons, promoted the formation of microvessels in the mouse brain by enhancing brain CD31, VEGF, N-cadherin, Ang-1. The new vessels promoted by BBR were observed to have a complete structure and perfect function, which in turn promoted the recovery of cerebral blood flow (CBF). In general, berberine is effective to 3×Tg AD mice, has a neuroprotective effect, and is a candidate drug for the multi-target prevention and treatment of AD.
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发表时间: 2016-05
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