MicroRNA-128-3p impaired water maze learning by suppressing Doublecortin expression in both wild type and Aβ-42 infused mice. (28th July 2016)

• Record Type: Journal Article
• Authors: Chen, Jinlong; Li, Wen; Li, Yuan; He, Songwei; Li, Lingyu; Liang, Lining; Song, Yancheng; Qin, Dajiang; Zheng, Hui
• Is Part Of: Neuroscience letters. Volume 626(2016)
• Page Start: 79
• Page End: 85
• Publication Date: 2016-07-28
• Subjects: 128-vir/con-vir/DCX-vir lentivirus encoding miR-128/control vector/Dcx -- Arpp21 cyclic AMP-regulated phosphoprotein -- DCX Doublecortin -- DCX-3′UTR/-mu wildtype/mutated 3′UTR of Dcx in 3′UTR of Renilla luciferase -- DG dentate gyrus -- miR-128 microRNA-128-3p -- MWM Morris Water Maze -- R3H domain containing 1 R3hdm1 -- SGZ subgranular zone; MiR-128 -- Doublecortin -- Neurogenesis -- Water Maze learning -- Aβ-42; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.05.031
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: miR-128 impaired neural stem cell differentiation by targeting Dcx . miR-128 impaired hippocampal-dependent water maze learning by targeting Dcx . miR-128-DCX axis also functions in mice infused with Aβ-42 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 14 days, 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.