Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease
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. Pol...
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doaj-50e5cec9c2464abea72260481f1fc0162020-11-24T21:43:16ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122017-11-01810.3389/fphar.2017.00805305147Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s DiseaseTomoharu Kuboyama0Keisuke Hirotsu1Tetsuya Arai2Hiroo Yamasaki3Chihiro Tohda4Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Toyama, JapanR&D Center, Kobayashi Pharmaceutical Co., Ltd., Ibaraki, JapanR&D Center, Kobayashi Pharmaceutical Co., Ltd., Ibaraki, JapanR&D Center, Kobayashi Pharmaceutical Co., Ltd., Ibaraki, JapanDivision of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Toyama, JapanMemory 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.http://journal.frontiersin.org/article/10.3389/fphar.2017.00805/fullAlzheimer’s diseasePolygalae Radixaxon degenerationamyloid βendocytosisgrowth cone collapse |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tomoharu Kuboyama Keisuke Hirotsu Tetsuya Arai Hiroo Yamasaki Chihiro Tohda |
spellingShingle |
Tomoharu Kuboyama Keisuke Hirotsu Tetsuya Arai Hiroo Yamasaki Chihiro Tohda Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease Frontiers in Pharmacology Alzheimer’s disease Polygalae Radix axon degeneration amyloid β endocytosis growth cone collapse |
author_facet |
Tomoharu Kuboyama Keisuke Hirotsu Tetsuya Arai Hiroo Yamasaki Chihiro Tohda |
author_sort |
Tomoharu Kuboyama |
title |
Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease |
title_short |
Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease |
title_full |
Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease |
title_fullStr |
Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease |
title_full_unstemmed |
Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer’s Disease |
title_sort |
polygalae radix extract prevents axonal degeneration and memory deficits in a transgenic mouse model of alzheimer’s disease |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2017-11-01 |
description |
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. |
topic |
Alzheimer’s disease Polygalae Radix axon degeneration amyloid β endocytosis growth cone collapse |
url |
http://journal.frontiersin.org/article/10.3389/fphar.2017.00805/full |
work_keys_str_mv |
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