期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 52, 期 1, 页码 113-126出版社
IOS PRESS
DOI: 10.3233/JAD-151126
关键词
Alzheimer's disease; APP23 mice; cerebrovascular remodeling; chronic cerebral hypoperfusion; galantamine; neurovascular unit; neurovascular trophic coupling
资金
- Research Committees from the Ministry of Health, Labour and Welfare of Japan [25293202, 15K09316, 15K15527, 15K21181]
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 alpha 7 subunit of nicotinic acetylcholine receptors (alpha 7-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.
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