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Morris Water Maze Test: Optimization for Mouse Strain and Testing Environment
Published on: June 22, 2015
MicroRNA-128-3p impaired water maze learning by suppressing Doublecortin expression in both wild type and Aβ-42
Jinlong Chen1, Wen Li1, Yuan Li1
1CAS 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.
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.
Insights
MicroRNA-128 (miR-128) suppresses Doublecortin (Dcx) expression, impacting neural stem cell differentiation and hippocampus-dependent learning. This miR-128-Dcx axis is crucial for cognitive function and affected by amyloid-beta in Alzheimer's models.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNA-128 (miR-128) is abundant in the brain and targets Doublecortin (Dcx), a critical factor in adult neurogenesis.
- The precise physiological consequences of the miR-128-Dcx interaction in vivo are not fully understood.
Purpose of the Study:
- To elucidate the functional role of the miR-128-Dcx regulatory axis in neurogenesis and hippocampus-dependent learning.
- To investigate the involvement of this axis in an Alzheimer's disease model.
Main Methods:
- Utilized lentivirus systems for overexpressing miR-128 and Dcx in neural stem cells and mouse hippocampi.
- Assessed neurogenesis by quantifying TuJ+ cells.
- Evaluated learning and memory using the water maze task.
- Induced an Alzheimer's-like state using Aβ-42 infusion.
Main Results:
- miR-128 directly suppressed Dcx expression by binding to its 3'UTR.
- Overexpression of miR-128 inhibited neural stem cell differentiation and impaired water maze learning.
- Simultaneous Dcx restoration attenuated miR-128-induced learning deficits.
- Alzheimer's model (Aβ-42 infusion) showed increased miR-128, decreased Dcx, and learning impairments, partially reversed by Dcx overexpression.
Conclusions:
- The miR-128-Dcx regulatory axis is essential for normal hippocampus-dependent learning.
- Dysregulation of this axis contributes to cognitive deficits in an Alzheimer's disease model.
- Targeting the miR-128-Dcx pathway may offer therapeutic potential for cognitive impairment.
