[MiR-124 ameliorates MK-801-induced anxiety-like behaviors in mice by promoting hippocampal neural stem cell proliferation and differentiation].

Abstract

Objectives: To investigate the regulatory effect of miR-124 on MK-801-induced anxiety-like behavior in mice.

Methods: Sixty 6-week-old male C57BL/6J mice were randomly divided into control group, MK-801+Saline group, MK-801+Vehicle group, and MK-801+miR-124 group (n=15). Anxiety-like models were established in the latter 3 groups by intraperitoneal injection of MK-801, and stereotaxic brain injection of mmu-miR-124-3p mimics was performed for local miR-124 overexpression in the hippocampus, and successful miR-124 transfection was verified using RT-qPCR. Behavioral tests were conducted to assess the effect of miR-124 overexpression on anxiety-like behaviors of the mice. Western blotting and immunofluorescence staining were used to examine the effects of miR-124 overexpression on hippocampal neuronal protein expressions, neural stem cell number, number of new neurons, and neuronal differentiation.

Results: The mice in MK-801+miR-124 group showed significantly increased hippocampal miR-124 levels after the injection. The mice receiving miR-124 microinjection exhibited significant increases in both the total and central zone distance traveled in open field test and in percentages of time spent in the open arms in elevated plus maze test. Hippocampal Tuj1 protein expression and the numbers of hippocampal neural stem cells and newborn neurons, along with the fluorescence area ratio of newborn to mature neurons, increased significantly in the mice in MK-801+miR-124 group. Conclusion miR-124 overexpression ameliorates MK-801-induced anxiety-like behaviors in mice by promoting hippocampal neural stem cell proliferation and differentiation and increasing hippocampal neuron number, suggesting the value of miR-124 as a potential therapeutic target for anxiety disorders.