Strong Impact of Chronic Cerebral Hypoperfusion on Neurovascular Unit, Cerebrovascular Remodeling, and Neurovascular Trophic Coupling in Alzheimer’s Disease Model Mouse
Affiliations:
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Kitaku, Okayama, Japan
Correspondence:
[*]
Correspondence to: Prof. Koji Abe, Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmacy, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. Tel.: +81 86 235 7365; Fax: +81 86 235 7368; E-mail: shangjw2@gmail.com.
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.
