Effect of miR-124 on neuronal apoptosis in rats with cerebral infarction through Wnt/ß-catenin signaling pathway.

ABSTRACT

OBJECTIVE: The aim of this study was to observe the influence of micro ribonucleic acid (miR)-124 on neuronal apoptosis in rats with cerebral infarction (CI), and to further investigate the underlying mechanism of miR-124 in CI occurrence and development. MATERIALS AND METHODS: A total of 60 adult male Wistar rats were randomly divided into the Sham group, the CI group and the CI + miR-124 mimics group using a random number table. The focal CI model was established using the suture-occluded method. After successful modeling, miR-124 mimics were stereotactically injected into the lateral ventricle of rats. 24 h after operation, the neurological function of rats in each group was scored using modified neurological severity score (mNSS). Meanwhile, the infarction area of brain tissues was evaluated by the triphenyl tetrazolium chloride (TTC) method. The protein expression levels of apoptosis-related genes, including B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), C-Caspase and T-Caspase, were detected via Western blotting. The expression and location of caspase-3 in brain tissues were detected via immunofluorescence staining. Moreover, the level of apoptosis in each group was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. In addition, the expression levels of the Wnt/ß-catenin signaling pathway-related proteins were detected via Western blotting. RESULTS: Polymerase Chain Reaction (PCR) results revealed that the expression level of miR-124 in the CI group was significantly decreased when compared with that of the Sham group (p<0.05). The mNSS and TTC staining results manifested that injection of miR-124 mimics could significantly reduce the CI-induced neurological deficits and CI area (p<0.05). At the same time, the levels of Bax and C-caspase/T-Caspase were significantly decreased, whereas the expression of Bcl-2 was remarkably increased after the injection of miR-124 mimics (p<0.05). Besides, the number of apoptotic cells in the CI + miR-124 mimic group was remarkably decreased (p<0.05). In addition, miR-124 mimics significantly activated the expression levels of Wnt and ß-catenin (p<0.05). CONCLUSIONS: The inhibitory effect of miR-124 on neuronal apoptosis in CI rats is probably related to the activation of the Wnt/ß-catenin signaling pathway. Furthermore, miR-124 is expected to be a target drug for the clinical treatment of CI.