MiR-497 Regulates Neuronal Death in Mouse Brain After Transient Focal Cerebral Ischemia

Overview

Journal Neurobiol Dis

Specialty Neurology

Date 2010 Jan 8

PMID 20053374

Citations 168

Authors

Ke-Jie Yin

Zhen Deng

Huarong Huang

Milton Hamblin

Changqing Xie

Jifeng Zhang

Y Eugene Chen

Affiliations

Soon will be listed here.

Abstract

Dysfunction of the microRNA (miR) network has been emerging as a major regulator in neurological diseases. However, little is known about the functional significance of unique miRs in ischemic brain damage. Here, we found that miR-497 is induced in mouse brain after transient middle cerebral artery occlusion (MCAO) and mouse N2A neuroblastoma (N2A) cells after oxygen-glucose deprivation (OGD). Loss-of-miR-497 function significantly suppresses OGD-induced N2A cell death, whereas gain-of-miR-497 function aggravates OGD-induced neuronal loss. Moreover, miR-497 directly binds to the predicted 3'-UTR target sites of bcl-2/-w genes. Furthermore, knockdown of cerebral miR-497 effectively enhances bcl-2/-w protein levels in the ischemic region, attenuates ischemic brain infarction, and improves neurological outcomes in mice after focal cerebral ischemia. Taken together, our data suggest that miR-497 promotes ischemic neuronal death by negatively regulating antiapoptotic proteins, bcl-2 and bcl-w. We raise the possibility that this pathway may contribute to the pathogenesis of the ischemic brain injury in stroke.

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