Strong Impact of Chronic Cerebral Hypoperfusion on Neurovascular Unit, Cerebrovascular Remodeling, and Neurovascular Trophic Coupling in Alzheimer's Disease Model Mouse

Jingwei Shang, Toru Yamashita, Yun Zhai, Yumiko Nakano, Ryuta Morihara, Yusuke Fukui, Nozomi Hishikawa, Yasuyuki Ohta, Koji Abe

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Although chronic cerebral hypoperfusion (CCH) may affect Alzheimer's disease (AD) pathogenesis, the mechanism remains elusive. In the present study, we investigated the role of CCH on an AD mouse model in neurovascular unit, cerebrovascular remodeling, and neurovascular trophic coupling. Moreover, examined protective effect of galantamine. Alzheimer's disease transgenic mice (APP23) were subjected to bilateral common carotid arteries stenosis with ameroid constrictors for slowly progressive cerebral hypoperfusion. CCH exacerbated neuronal loss and decrease of α7 subunit of nicotinic acetylcholine receptors (α7-nAChRs) expression in hippocampus and thalamus at 12 months. Meanwhile, CCH greatly induced advanced glycation end products expression, and blood-brain barrier leakage through observing IgG and MMP9 expressions. Furthermore, a significant number of dramatic enlarged cerebral vessels with remodeling, BDNF/TrkB decreased in neurovascular trophic coupling. The present study demonstrated that CCH strongly enhanced primary AD pathology including neurodegeneration, neurovascular unit disruption, cerebrovascular remodeling and neurovascular trophic coupling damage in AD mice, and that galantamine treatment greatly ameliorated such neuropathologic abnormalities.

Original languageEnglish
Pages (from-to)113-126
Number of pages14
JournalJournal of Alzheimer's Disease
Volume52
Issue number1
DOIs
Publication statusPublished - Apr 26 2016

Keywords

  • APP23 mice
  • Alzheimer's disease
  • cerebrovascular remodeling
  • chronic cerebral hypoperfusion
  • galantamine
  • neurovascular trophic coupling © 2016 IOS Press and the authors. All rights reserved.
  • neurovascular unit

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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