Downregulation of lncRNA GAS5 prevents mitochondrial apoptosis and hypoxic-ischemic brain damage in neonatal rats through the microRNA-128-3p/Bax/Akt/GSK-3β axis

Objective Hypoxic/ischemic brain damage (HIBD) results in increased neonatal mortality and serious neurologic morbidity. Long noncoding RNAs (lncRNAs) are shown as essential modulators of various neurological diseases. Here, we determined the mechanisms of lncRNA GAS5 in mitochondrial apoptosis in HIBD rats. Methods The HIBD neonatal rat model was established and treated with shRNA-GAS5 or antagomir miR-128-3p. The morphological changes and apoptosis rate were observed by histological staining. Expressions of GAS5, miR-128-3p, and Bax mRNA in brain tissues of HIBD neonatal rats were determined. The binding relationships between GAS5 and miR-128-3p, and miR-128-3p and Bax were confirmed by dual-luciferase assay. Subsequently, the mitochondrial membrane potential and apoptosis-related factors in brain tissues of HIBD neonatal rats were detected. Western blot analysis was performed to detect the expression of Akt/GSK3 beta pathway-associated proteins. Results The neurons in the brain tissue of HIBD neonatal rats decreased with disordered arrangement, and showed vacuolization and nuclear pyknosis, obvious brain damage, increased neuronal apoptosis, and enhanced mitochondrial apoptotic pathway. Downregulated miR-128-3p and upregulated GAS5 and Bax mRNA were found in HIBD neonatal rats. There were binding relationships between GAS5 and miR-128-3p, and miR-128-3p and Bax mRNA. Inhibition of lncRNA GAS5 in HIBD neonatal rats suppressed mitochondrial apoptosis. miR-128-3p knockdown annulled the inhibitory effect of inhibiting lncRNA GAS5 on mitochondrial apoptosis. Silencing GAS5 increased the phosphorylation levels of Akt and GSK3 beta. Conclusion Downregulation of lncRNA GAS5 prevents mitochondrial apoptosis in neonatal HIBD rats by regulating the miR-128-3p/Bax/Akt/GSK-3 beta axis.

Automated summary

In neonatal HIBD rats, downregulation of lncRNA GAS5 prevents mitochondrial apoptosis by regulating the miR-128-3p/Bax/Akt/GSK-3 beta axis, which helps in the prevention of neurological damage.