title: Disruption of White Matter Integrity by Chronic Cerebral Hypoperfusion in Alzheimer's Disease Mouse Model.
abstract: A rapidly progressing aging society has raised attention to white matter lesions in Alzheimer's disease. In the present study, we applied an AD plus cerebral hypoperfusion (HP) mouse model and investigated the alternation of key protein molecules in the nodal, paranodal, and intermodal sites in the white matter as well as the efficacy of galantamine. Cerebral HP was induced in APP23 mice by bilateral common carotid arteries stenosis with ameroid constrictors. Compared with the wild type and simple APP23 mice, APP23 + HP mice showed a progressive loss of MAG and NF186 from 6 to 12 months, broken misdistribution of MBP, and extended relocation of Nav1.6 and AnkG beyond the primary nodal region in the corpus callosum. Such abnormal neuropathological processes were retrieved with galantamine treatment. The present study demonstrated that cerebral HP strongly disrupted white matter integrity (WMI) at intermodal, paranodal, and Ranvier's nodal sites which may be associated with cognitive decline. Galantamine treatment significantly protected such WMI probably by allosterically potentiating ligand action.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhai
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Nakano
authors.forename: Zhuoran
authors.initials: Z
authors.lastname: Sun
authors.forename: Ryuta
authors.initials: R
authors.lastname: Morihara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fukui
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hishikawa
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017487:Ankyrins / Q000032:analysis; D002545:Brain Ischemia / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000032:analysis; D003337:Corpus Callosum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D005702:Galantamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018992:Myelin-Associated Glycoprotein / Q000032:analysis; D009414:Nerve Growth Factors / Q000032:analysis; D018697:Nootropic Agents / Q000494:pharmacology; D066127:White Matter / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*
chemical_list: C094681:Ank3 protein, mouse; D017487:Ankyrins; D015815:Cell Adhesion Molecules; D018992:Myelin-Associated Glycoprotein; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D018697:Nootropic Agents; D005702:Galantamine
keywords: APP23 mice; Alzheimer’s disease; galantamine; hypoperfusion; white matter mater lesion