title: Identification of microRNAs involved in Alzheimer's progression using a rabbit model of the disease.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins in the brain. The vast majority of cases are late onset AD (LOAD), which are genetically heterogeneous and occur sporadically. High blood cholesterol is suggested to be a risk factor for this disease. Several neuropathological changes of LOAD can be reproduced by supplementing a rabbit's diet with 2% cholesterol for 12 weeks. Accumulating data in the literature suggest that microRNAs (miRNA) participate in the development of AD pathology. The present study focuses on the survey of changes of miRNA expression in rabbit brains during the progression of AD-like pathology using microarray followed by Taq-Man qRT-PCR analyses. Out of 1769 miRNA probes used in the experiments, 99 miRNAs were found to be present in rabbit brain, 57 were newly identified as miRNAs from rabbit brain. Eleven miRNAs showed significant changes over AD-like pathology progression. Among them, the changes of miR-125b, miR-98, miR-107, miR-30, along with 3 members of the let-7 family were similar to those observed in human AD samples, whereas the expression patterns of miR-15a, miR-26b, miR-9 and miR-576-3p were unique to this rabbit LOAD model. The significant up regulation of miR-26b is consistent with the decrease of leptin levels in the brains of cholesterol fed rabbit model for AD, confirming that miR-26b is indeed regulated by leptin and that both leptin and miR-26b may be involved in cholesterol induced AD-like pathology.
authors.affiliation: Human Health and Therapeutics, National Research Council of Canada Ottawa, Ontario, Canada K1A 0R6 ; Faculties of Medicine, University of Ottawa Ottawa, Ontario, Canada, K1H 8M5.
authors.forename: Qing Yan
authors.initials: QY
authors.lastname: Liu
authors.affiliation: Faculties of Medicine, University of Ottawa Ottawa, Ontario, Canada, K1H 8M5.
authors.forename: Marilyn N Vera
authors.initials: MN
authors.lastname: Chang
authors.affiliation: Human Health and Therapeutics, National Research Council of Canada Ottawa, Ontario, Canada K1A 0R6.
authors.forename: Joy X
authors.initials: JX
authors.lastname: Lei
authors.affiliation: Human Health and Therapeutics, National Research Council of Canada Ottawa, Ontario, Canada K1A 0R6.
authors.forename: Roger
authors.initials: R
authors.lastname: Koukiekolo
authors.affiliation: Human Health and Therapeutics, National Research Council of Canada Ottawa, Ontario, Canada K1A 0R6.
authors.forename: Brandon
authors.initials: B
authors.lastname: Smith
authors.affiliation: Human Health and Therapeutics, National Research Council of Canada Ottawa, Ontario, Canada K1A 0R6.
authors.forename: Dongling
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota Grand Forks, ND 58202, USA.
authors.forename: Othman
authors.initials: O
authors.lastname: Ghribi
keywords: Alzheimer’s disease; Let-7; MicroRNA; leptin; miR-26b; rabbit AD model
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