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 language | English |
|---|---|
| Pages (from-to) | 113-126 |
| Number of pages | 14 |
| Journal | Journal of Alzheimer's Disease |
| Volume | 52 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 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
