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Alzheimer's Disease, Other Dementia, Aging

開催日 2014/9/11
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Integrated analysis among miRNA/mRNA expression in the brain of Alzheimer's model mouse and the target mRNA profiles by RIP-Chip

  • P1-285
  • 檜垣 小百合 / Sayuri Higaki:1 村松 昌 / Masashi Muramatsu:1,2 松田 明生 / Akio Matsuda:3 松本 建治 / Kenji Matsumoto:3 道川 誠 / Makoto Michikawa:4,5 新飯田 俊平 / Shumpei Niida:1 
  • 1:国立長寿医療セ・バイオバンクオミックス / BioBank Omics Unit, Natl Cent Geriat Gerontol, Aichi, Japan 2:Dept Cancer Genet, Roswell Park Cancer Inst, Buffalo, USA / Dept Cancer Genet, Roswell Park Cancer Inst, Buffalo, USA 3:国立成育医療セ研究所・免疫アレルギー / Dept Immunol Allergy, Natl Res Inst Child Health Dev, Tokyo, Japan 4:国立長寿医療セ・アルツハイマー / Dept Alzheimers Dis Res, Natl Cent Geriat Gerontol, Aichi, Japan 5:名古屋市大医・生化学 / Dept Biochem, Grad Med Sci, Nagoya City Univ, Aichi, Japan 

MicroRNA (miRNA)s are small noncoding regulatory RNA molecules that fine tune post-transcriptional gene expression of the cell. Altered miRNA profiles could be both a cause and a consequence of neurodegenerative disorders such as Alzheimer's disease (AD). However, little is known about the roles of miRNA involved in pathology of AD. We performed miRNA and mRNA microarray analysis in the frontal cortex of Tg2576 transgenic mouse overexpressing human mutations of the amyloid-β precursor protein (APP). As a result, miR-200 family (miR-200a, -141, -429, -200b, -200c) upregulated at 10 month old (mo); increasing phase for Aβ level, but not at 17 mo; plateau phase for Aβ level in APP mouse. In primary neuronal cells, the expression levels of miR-200b/c were also increased following Aβ1-42 stimulation. Moreover, primary neurons co-transfected miR-200b/c significantly reduced Aβ secretion into conditioned medium. The upregulation of miR-200 family was inferred to be a defensive or suppressive response to Aβ toxicity. To elucidate miR-200b/c signaling pathways to Aβ, we searched their direct targets through RIP (ribonucleoprotein immunoprecipitation) on chip. RIP-Chip assay can biochemically identify target mRNAs which are isolated from co-immunoprecipitation with a ribonucleoprotein, Argonaute2 followed by microarray analysis. Immunoprecipitated targets of miR-200b/c (Fold change >2.0, t-test; p<0.05) included SIRT1, PRDX2 and JUN which were upstream of differentially expressed mRNAs (DEM) (Fold change >1.5, t-test; p<0.05) in the cortex of 10-mo. APP mouse. In fact, the Ingenuity Pathway Analysis showed a well-combined network including PI3K, ERK1/2 and CREB pathway between target mRNA and DEM. These findings provide insights into the regulation of miR-200b/c to Aβ production via PI3K pathway.

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