Chronic cerebral hypoperfusion alters amyloid-β transport related proteins in the cortical blood vessels of Alzheimer's disease model mouse

Jingwei Shang, Toru Yamashita, Feng Tian, Xianghong Li, Xia Liu, Xiaowen Shi, Yumiko Nakano, Keiichiro Tsunoda, Emi Nomura, Ryo Sasaki, Koh Tadokoro, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Abnormal accumulation of amyloid-β (Aβ) peptide defines progression of Alzheimer's disease (AD) pathology in brain. Here, we investigated expressive changes of two main Aβ transport receptors low-density lipoprotein receptor related protein-1 (LRP1) and receptor for advanced glycation end products (RAGE) in a novel AD mice (APP23) with chronic cerebral hypoperfusion (CCH) model, moreover, examined a protective effect of a free radical scavenger edaravone (Eda). In contrast to wild type (WT) and APP23 mice, CCH strongly accelerated abnormal Aβ40 depositions and cerebral amyloid angiopathy (CAA) pathology, increased both LRP1 and RAGE expressions in brain parenchyma, while a decrease of LRP1 and an increase of RAGE were observed in vascular endothelial cells at age 12 months (M) of AD mice. Furthermore, CCH strongly increased expressions of two hypoxia-related proteins hypoxia inducible factor-1α (HIF-1α) and heme oxygenase-1 (HO-1), two oxidative-related proteins 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG), and decreased both two vital nutrient transporter proteins major facilitator super family domain containing 2a (Mfsd2a) and glucose transporter 1 (Glut1) expressions. Such the above abnormal pathological changes were significantly ameliorated by edaravone treatment. The present study demonstrated that CCH strongly enhanced primary AD pathology causing double imbalances of Aβ efflux and influx transport related proteins in the cortical blood vessels in AD mice, and that such a neuropathologic abnormality was greatly ameliorated by Eda.

Original languageEnglish
Article number146379
JournalBrain Research
Volume1723
DOIs
Publication statusPublished - Nov 15 2019

Fingerprint

Amyloid
Blood Vessels
Carrier Proteins
Alzheimer Disease
Lipoprotein Receptors
Pathology
Proteins
Low Density Lipoprotein Receptor-Related Protein-1
Cerebral Amyloid Angiopathy
Hypoxia-Inducible Factor 1
Free Radical Scavengers
Heme Oxygenase-1
Facilitative Glucose Transport Proteins
Brain
Endothelial Cells
Food
Peptides
Advanced Glycosylation End Product-Specific Receptor
phenylmethylpyrazolone

Keywords

  • Alzheimer's disease
  • Amyloid-β transport
  • Chronic cerebral hypoperfusion
  • Edaravone

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Chronic cerebral hypoperfusion alters amyloid-β transport related proteins in the cortical blood vessels of Alzheimer's disease model mouse. / Shang, Jingwei; Yamashita, Toru; Tian, Feng; Li, Xianghong; Liu, Xia; Shi, Xiaowen; Nakano, Yumiko; Tsunoda, Keiichiro; Nomura, Emi; Sasaki, Ryo; Tadokoro, Koh; Sato, Kota; Takemoto, Mami; Hishikawa, Nozomi; Ohta, Yasuyuki; Abe, Koji.

In: Brain Research, Vol. 1723, 146379, 15.11.2019.

Research output: Contribution to journalArticle

Shang, Jingwei ; Yamashita, Toru ; Tian, Feng ; Li, Xianghong ; Liu, Xia ; Shi, Xiaowen ; Nakano, Yumiko ; Tsunoda, Keiichiro ; Nomura, Emi ; Sasaki, Ryo ; Tadokoro, Koh ; Sato, Kota ; Takemoto, Mami ; Hishikawa, Nozomi ; Ohta, Yasuyuki ; Abe, Koji. / Chronic cerebral hypoperfusion alters amyloid-β transport related proteins in the cortical blood vessels of Alzheimer's disease model mouse. In: Brain Research. 2019 ; Vol. 1723.
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AU - Shang, Jingwei

AU - Yamashita, Toru

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AU - Li, Xianghong

AU - Liu, Xia

AU - Shi, Xiaowen

AU - Nakano, Yumiko

AU - Tsunoda, Keiichiro

AU - Nomura, Emi

AU - Sasaki, Ryo

AU - Tadokoro, Koh

AU - Sato, Kota

AU - Takemoto, Mami

AU - Hishikawa, Nozomi

AU - Ohta, Yasuyuki

AU - Abe, Koji

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