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ID 57249
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Author
Liu, Xia Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yamashita, Toru Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ORCID Kaken ID
Shang, Jingwei Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Shi, Xiaowen Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Morihara, Ryuta Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Huang, Yong Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sato, Kota Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences ORCID
Takemoto, Mami Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University ORCID
Hishikawa, Nozomi Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID
Ohta, Yasuyuki Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID researchmap
Abe, Koji Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kaken ID researchmap
Abstract
BACKGROUND:
Multiple pathogeneses are involved in Alzheimer's disease (AD), such as amyloid-β accumulation, neuroinflammation, and oxidative stress. The pathological impact of chronic cerebral hypoperfusion on Alzheimer's disease is still poorly understood.
METHODS:
APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive chronic cerebral hypoperfusion (CCH). The effects of the administration of Twendee X (TwX) were evaluated by behavioral analysis, immunohistochemical analysis, and immunofluorescent histochemistry.
RESULTS:
In the present study, chronic cerebral hypoperfusion, which is commonly found in aged Alzheimer's disease, significantly exacerbated motor dysfunction of APP23 mice from 5 months and cognitive deficit from 8 months of age, as well as neuronal loss, extracellular amyloid-β plaque and intracellular oligomer formations, and amyloid angiopathy at 12 months. Severe upregulations of oxidative markers and inflammatory markers were found in the cerebral cortex, hippocampus, and thalamus at 12 months. Twendee X treatment (20 mg/kg/d, from 4.5 to 12 months) substantially rescued the cognitive deficit and reduced the above amyloid-β pathology and neuronal loss, alleviated neuroinflammation and oxidative stress.
CONCLUSIONS:
The present findings suggested a potential therapeutic benefit of Twendee X for Alzheimer's disease with chronic cerebral hypoperfusion.
Keywords
APP23 mice
Alzheimer's disease
anti-inflammatory
antioxidative
chronic cerebral hypoperfusion
Note
This fulltext will be available in Jun 2020
Published Date
2019-07-31
Publication Title
Journal of Stroke and Cerebrovascular Diseases
Volume
volume28
Issue
issue7
Publisher
Elsevier
Start Page
1993
End Page
2002
ISSN
10523057
NCID
AA10780852
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
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DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.029
License
https://creativecommons.org/licenses/by-nc-nd/4.0/
Citation
Xia Liu, Toru Yamashita, Jingwei Shang, Xiaowen Shi, Ryuta Morihara, Yong Huang, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe, Clinical and Pathological Benefit of Twendee X in Alzheimer's Disease Transgenic Mice with Chronic Cerebral Hypoperfusion, Journal of Stroke and Cerebrovascular Diseases, Volume 28, Issue 7, 2019, Pages 1993-2002, ISSN 1052-3057, https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.03.029.
Open Access (Publisher)
non-OA
Open Archive (publisher)
Non-OpenArchive