Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.
Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease.
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DOI：
10.3389/fphar.2017.00805
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发表时间：
2017
影响因子：
5.6
通讯作者：
Tohda C
中科院分区：
文献类型：
--
作者：
Kuboyama T;Hirotsu K;Arai T;Yamasaki H;Tohda C
阿尔茨海默病（AD）的记忆障碍是由于轴突退化和神经网络中断而发生的。由于在神经网络破坏后只有有限的恢复可能，因此在疾病进展的早期阶段预防轴突变性对于预防AD是必要的。远志（Polygala tenuifolia的根; PR）是一种用于镇静和遗忘的传统草药。在这项研究中，我们的目的是澄清和分析PR对记忆缺陷的预防作用，在转基因AD小鼠模型，5XFAD。5XFAD小鼠在5月龄时表现出记忆缺陷。因此，将远志的水提取物（PR提取物）口服给药至未显示记忆损伤迹象的4月龄5XFAD小鼠。连续给药56天后，PR提取物可预防与5XFAD小鼠嗅周皮质中淀粉样蛋白β（Aβ）斑块积聚相关的认知缺陷和轴突变性。PR提取物不影响5XFAD小鼠脑中Aβ斑块的形成。在培养的神经元中，PR提取物可防止Aβ诱导的轴突生长锥塌陷和轴突萎缩。此外，它阻止Aβ诱导的内吞作用在培养的神经元的生长锥。我们以前的研究报道，内吞抑制足以防止Aβ诱导的生长锥塌陷、轴突变性和记忆障碍。因此，PR提取物可能通过抑制内吞作用防止轴突变性和记忆障碍。PR是第一个预防AD的候选药物，可抑制神经元的内吞作用。
Memory impairments in Alzheimer’s disease (AD) occur due to degenerated axons and disrupted neural networks. Since only limited recovery is possible after the destruction of neural networks, preventing axonal degeneration during the early stages of disease progression is necessary to prevent AD. Polygalae Radix (roots of Polygala tenuifolia; PR) is a traditional herbal medicine used for sedation and amnesia. In this study, we aimed to clarify and analyze the preventive effects of PR against memory deficits in a transgenic AD mouse model, 5XFAD. 5XFAD mice demonstrated memory deficits at the age of 5 months. Thus, the water extract of Polygalae Radix (PR extract) was orally administered to 4-month-old 5XFAD mice that did not show signs of memory impairment. After consecutive administrations for 56 days, the PR extract prevented cognitive deficit and axon degeneration associated with the accumulation of amyloid β (Aβ) plaques in the perirhinal cortex of the 5XFAD mice. PR extract did not influence the formation of Aβ plaques in the brain of the 5XFAD mice. In cultured neurons, the PR extract prevented axonal growth cone collapse and axonal atrophy induced by Aβ. Additionally, it prevented Aβ-induced endocytosis at the growth cone of cultured neurons. Our previous study reported that endocytosis inhibition was enough to prevent Aβ-induced growth cone collapse, axonal degeneration, and memory impairments. Therefore, the PR extract possibly prevented axonal degeneration and memory impairment by inhibiting endocytosis. PR is the first preventive drug candidate for AD that inhibits endocytosis in neurons.
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影响因子：
4.1
作者：
Killin LO;Starr JM;Shiue IJ;Russ TC
通讯作者：
Russ TC
影响因子：
2
作者：
Naito, Rie;Tohda, Chihiro
通讯作者：
Tohda, Chihiro
影响因子：
3.3
作者：
BENES, FM;FAROL, PA;BIRD, ED
通讯作者：
BIRD, ED
影响因子：
2.5
作者：
Jia, HX;Jiang, Y;Zhang, D
通讯作者：
Zhang, D
影响因子：
4.2
作者：
Park, CH;Choi, SH;Suh, YH
通讯作者：
Suh, YH