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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, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University 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 publons researchmap
Abstract
BACKGROUND:
The pathological impact of chronic cerebral hypoperfusion (CCH) on Alzheimer's disease (AD) is still poorly understood. In the present study, we investigated the role of CCH on an AD mouse model in phosphorylated tau and α-synuclein pathology, neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of a new antioxidant Twendee X (TwX).
METHODS:
APP23 mice were implanted to bilateral common carotid arteries stenosis with ameroid constrictors to gradually decrease the cerebral blood flow. The effects of the administration of TwX were evaluated by immunohistochemical analysis and Immunofluorescent histochemistry.
RESULTS:
The present study revealed that the expressions of phospho-tau and phospho-α-synuclein were significantly increased in the APP23 + CCH mice group as compared with wild type and APP23 mice groups (*P < .05 and ⁎⁎P < .01 versus WT; #P < .05 and ##P < .01 versus APP23). In addition, CCH significantly exacerbated MMP-9 activation relating to blood-brain barrier destruction (⁎⁎P < .01 versus WT; #P < .05, and ##P < .01 versus APP23), enhanced neurovascular remodeling, and impaired a neurovascular trophic coupling in the vascular endothelial BDNF expression of the APP23 + CCH group. TwX treatment (20 mg/kg/day, from 4.5 to 12 months) significantly reduced tau and α-synuclein pathologies, ameliorated neurovascular dysfunction compared with APP23 + CCH group.
CONCLUSIONS:
Our findings indicate that administration of a new antioxidative mixture TwX substantially reduced the above neuropathologic abnormalities, suggesting a potential therapeutic benefit of TwX for AD with CCH.
Keywords
APP23 mice
Alzheimer's disease
chronic cerebral hypoperfusion
neurovascular dysfunction
phosphorylated tau
α-synuclein
Published Date
2019-10-31
Publication Title
Journal of Stroke and Cerebrovascular Diseases
Volume
volume28
Issue
issue10
Publisher
Elsevier
Start Page
104310
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.2019.104310
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, Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion, Journal of Stroke and Cerebrovascular Diseases, Volume 28, Issue 10, 2019, 104310, ISSN 1052-3057, https://doi.org/10.1016/j.jstrokecerebrovasdis.2019.104310.
Open Access (Publisher)
non-OA
Open Archive (publisher)
Non-OpenArchive