Hypoxic Postconditioning Offers Neuroprotection Against Transient Cerebral Ischemia via Down-Regulation of rno_piR_011022.

BACKGROUND

Piwi-interacting RNAs (piRNAs) are differentially expressed after cerebral ischemia. However, little is known about their roles in transient global cerebral ischemia (tGCI). Herein, we aim to elucidate the roles and the underlying molecular mechanisms of piRNAs in tGCI and cerebral ischemic tolerance induced by hypoxic postconditioning (HPC).

METHODS

The male rat models of tGCI and HPC were established in vivo. Oxygen-glucose deprivation/reoxygenation (OGD/R) was developed from primary hippocampal neurons in vitro. RNA-sequencing, fluorescence in situ hybridization, and quantitative real-time PCR were used for detecting piRNA expression. Immunohistochemistry, TUNEL staining, CCK8 assay, etc., were used to evaluate neuronal damage. Western blot was used to measure protein levels of NR2B, PSD95, and cleaved-caspase 3.

RESULTS

The expression profiles of piRNAs in CA1 were significantly changed after tGCI. HPC downregulated the expression of the top 5 piRNAs associated with synaptic function. Notably, the knockdown of rno_piR_011022 not only alleviated neuronal apoptosis and enhanced synaptic plasticity after tGCI and OGD/R but also reduced methyl-D-aspartate (NMDA) receptor 2B (NR2B) expression and inhibited NR2B-postsynaptic density 95 (PSD95) interaction following tGCI. HPC enhanced these inhibitory effects.

CONCLUSION

This innovative study indicated that the down-regulation of rno_piR_011022 plays an important role in HPC-mediated neuroprotection against tGCI through inhibiting the NR2B-PSD95 interaction.