title: MicroRNA-128-3p impaired water maze learning by suppressing Doublecortin expression in both wild type and Aβ-42 infused mice.
abstract: MicroRNA-128-3p (miR-128) is a brain-enriched microRNA reported to target Doublecortin (Dcx), a key transcriptional factor during adult neurogenesis. However, the downstream physiological effects of this miR-128-DCX axis remain unclear. Here we demonstrated that miR-128 could suppress Dcx expression by complementally binding to the -849 to -856 region of the 3'UTR of mouse Dcx. During differentiation of neural stem cells, over-expressing miR-128 with a lentivirus system inhibited the up-regulation of Dcx on Day 5, subsequently decreasing the percentage of TuJ+ cells on Day 16. Administration of the lentivirus encoding miR-128 into mouse hippocampi significantly impaired water maze learning after 14days, which could be attenuated when the Dcx-encoding virus was delivered simultaneously. In addition, similar changes including miR-128 up-regulation, Dcx down-regulation and learning defects were observed after a 14-day infusion of Aβ-42, which were also partially reversed by over-expressing Dcx. Collectively, the regulation axis from miR-128 to Dcx is critical for hippocampus-related contextual learning not only in wild type, but also in mice infused with Aβ-42.
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Songwei
authors.initials: S
authors.lastname: He
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Anhui University, Hefei 230601, China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Liang
authors.affiliation: The third hospital, Southern Medical University, #183 Zhongshan Ave. E., Guangzhou 510665, China.
authors.forename: Yancheng
authors.initials: Y
authors.lastname: Song
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: qin_dajiang@gibh.ac.cn.
authors.forename: Dajiang
authors.initials: D
authors.lastname: Qin
authors.affiliation: CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: zheng_hui@gibh.ac.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D000818:Animals; D002454:Cell Differentiation; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005822:Genetic Vectors; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D016086:Lentivirus / Q000502:physiology; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology; D055495:Neurogenesis; D009479:Neuropeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage*
chemical_list: D020413:3' Untranslated Regions; D016229:Amyloid beta-Peptides; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C550324:Mirn128 microRNA, mouse; D009479:Neuropeptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)
keywords: Aβ-42; Doublecortin; MiR-128; Neurogenesis; Water Maze learning