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.
| Original language | English |
|---|---|
| Article number | 104310 |
| Journal | Journal of Stroke and Cerebrovascular Diseases |
| Volume | 28 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2019 |
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Keywords
- Alzheimer's disease
- APP23 mice
- chronic cerebral hypoperfusion
- neurovascular dysfunction
- phosphorylated tau
- α-synuclein
ASJC Scopus subject areas
- Surgery
- Rehabilitation
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Cite this
Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion. / Liu, Xia; Yamashita, Toru; Shang, Jingwei; Shi, Xiaowen; Morihara, Ryuta; Huang, Yong; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi; Ohta, Yasuyuki; Abe, Koji.
In: Journal of Stroke and Cerebrovascular Diseases, Vol. 28, No. 10, 104310, 01.10.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Twendee X Ameliorates Phosphorylated Tau, α-Synuclein and Neurovascular Dysfunction in Alzheimer's Disease Transgenic Mice With Chronic Cerebral Hypoperfusion
AU - Liu, Xia
AU - Yamashita, Toru
AU - Shang, Jingwei
AU - Shi, Xiaowen
AU - Morihara, Ryuta
AU - Huang, Yong
AU - Sato, Kota
AU - Takemoto, Mami
AU - Hishikawa, Nozomi
AU - Ohta, Yasuyuki
AU - Abe, Koji
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - APP23 mice
KW - chronic cerebral hypoperfusion
KW - neurovascular dysfunction
KW - phosphorylated tau
KW - α-synuclein
UR - http://www.scopus.com/inward/record.url?scp=85072545723&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85072545723&partnerID=8YFLogxK
U2 - 10.1016/j.jstrokecerebrovasdis.2019.104310
DO - 10.1016/j.jstrokecerebrovasdis.2019.104310
M3 - Article
C2 - 31383622
AN - SCOPUS:85072545723
VL - 28
JO - Journal of Stroke and Cerebrovascular Diseases
JF - Journal of Stroke and Cerebrovascular Diseases
SN - 1052-3057
IS - 10
M1 - 104310
ER -