Disruption of White Matter Integrity by Chronic Cerebral Hypoperfusion in Alzheimer's Disease Mouse Model

Yun Zhai, Toru Yamashita, Yumiko Nakano, Zhuoran Sun, Ryuta Morihara, Yusuke Fukui, Yasuyuki Ohta, Nozomi Hishikawa, Koji Abe

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1311-1319
Number of pages9
JournalJournal of Alzheimer's Disease
Volume52
Issue number4
DOIs
Publication statusPublished - 2016

Fingerprint

Galantamine
Alzheimer Disease
Corpus Callosum
Carotid Stenosis
Ligands
White Matter
Therapeutics
Proteins

Keywords

  • Alzheimer's disease
  • APP23 mice
  • galantamine
  • hypoperfusion
  • white matter mater lesion

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Disruption of White Matter Integrity by Chronic Cerebral Hypoperfusion in Alzheimer's Disease Mouse Model. / Zhai, Yun; Yamashita, Toru; Nakano, Yumiko; Sun, Zhuoran; Morihara, Ryuta; Fukui, Yusuke; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji.

In: Journal of Alzheimer's Disease, Vol. 52, No. 4, 2016, p. 1311-1319.

Research output: Contribution to journalArticle

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