title: Strong Impact of Chronic Cerebral Hypoperfusion on Neurovascular Unit, Cerebrovascular Remodeling, and Neurovascular Trophic Coupling in Alzheimer's Disease Model Mouse.
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.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shang
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Ryuta
authors.initials: R
authors.lastname: Morihara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fukui
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hishikawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005702:Galantamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D000069336:Neurovascular Coupling / Q000187:drug effects / Q000502:physiology*; D018697:Nootropic Agents / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D011978:Receptors, Nicotinic; D005702:Galantamine
keywords: APP23 mice; Alzheimer’s disease; cerebrovascular remodeling; chronic cerebral hypoperfusion; galantamine; neurovascular trophic coupling; neurovascular unit