The role of miR-182 in regulating pineal CLOCK expression after hypoxia-ischemia brain injury in neonatal rats

Abstract

Circadian rhythm disorder is a common neurological deficit caused by neonatal hypoxic-ischemic brain damage (HIBD). However, little is known about its underlying mechanisms. Our previous studies revealed a significant elevation of clock genes at the protein, but not mRNA, levels in the pineal gland after neonatal HIBD. To investigate the mechanisms of post-transcriptional regulation on clock genes, we screened changes of miRNA levels in the pineal gland after neonatal HIBD using high-throughput arrays. Within the miRNAs whose expression was significantly down-regulated, we identified one miRNA (miR182) that targeted the 3′-untranslated region (3′-UTR) of Clock, a key component of clock genes, and played a crucial role in regulating CLOCK expression after oxygen–glucose deprivation in primarily cultured pinealocytes. Our findings therefore provide new insight on studies of therapeutic targets for circadian rhythm disturbance after neonatal HIBD.