PPARγ agonist pioglitazone improves cerebellar dysfunction at pre-Aβ deposition stage in APPswe/PS1dE9 Alzheimer's disease model mice

Junya Toba, Miyu Nikkuni, Masato Ishizeki, Aya Yoshii, Naoto Watamura, Takafumi Inoue, Toshio Ohshima

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Alzheimer's disease (AD) is one of the best known neurodegenerative diseases; it causes dementia and its pathological features include accumulation of amyloid β (Aβ) and neurofibrillary tangles (NFTs) in the brain. Elevated Cdk5 activity and CRMP2 phosphorylation have been reported in the brains of AD model mice at the early stage of the disease, but the significance thereof in human AD remains unelucidated. We have recently reported that Aβ accumulation in the cerebellum of AD model APPswe/PS1dE9 (APP/PS1) mice, and cerebellar dysfunctions, such as impairment of motor coordination ability and long-term depression (LTD) induction, at the pre-Aβ accumulation stage. In the present study, we found increased phosphorylation levels of CRMP2 as well as increased p35 protein levels in the cerebellum of APP/PS1 mice. Interestingly, we show that pioglitazone, an agonist of peroxisome proliferator-activated receptor γ, normalized the p35 protein and CRMP2 phosphorylation levels in the cerebellum. Impaired motor coordination ability and LTD in APP/PS1 mice were ameliorated by pioglitazone treatment at the pre-Aβ accumulation stage. These results suggest a correlation between CRMP2 phosphorylation and AD pathophysiology, and indicate the effectiveness of pioglitazone treatment at the pre-Aβ accumulation stage in AD model mice.

    Original languageEnglish
    Pages (from-to)1039-1044
    Number of pages6
    JournalBiochemical and Biophysical Research Communications
    Volume473
    Issue number4
    DOIs
    Publication statusPublished - 2016 May 13

    Keywords

    • Alzheimer's disease
    • Cerebellum
    • CRMP
    • Mouse
    • Protein phosphorylation

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Cell Biology
    • Molecular Biology

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