Citation

Chen W, Zhao L, Zhang J, Wang B, Xu G, Lin C, Liu N. J. Chem. Neuroanat. 2019; 99: 1-8.

Affiliation

Department of the Neurosurgery, the First Affiliated Hospital of Nanjing Medical University, No 300, Guangzhou Road, Nanjing, 210029, Jiangsu, China. Electronic address: zl_nirvana@126.com.

Copyright

(Copyright © 2019, Elsevier Publishing)

DOI

10.1016/j.jchemneu.2019.05.003

PMID

31096001

Abstract

We have previously found that connexin43 is phosphorylated by extracellular-signal-regulated kinase (ERK)1/2 in rats of cerebral ischemia. Here, we investigated the potential roles of microRNA (miR)-302 cluster in the regulation of ERK1/2 mediated connexin43 phosphorylation and protection from traumatic brain injury (TBI) induced brain damage. We examined apoptosis and ERK1/2 and connexin43 phosphorylation in SH-SY5Y cells undergoing pulsatile shear stress treatment. We assessed expression of miR-302 cluster members and exogenously expressed miR-302 cluster in stressed cells to determine its effect on ERK1/2 and connexin43 phosphorylation. Finally, we investigated the effects of elevated miR-302 expression on cognitive function and brain damage in TBI rats generated by the controlled cortical impact method. Pulsatile shear stress leads to increased apoptosis and upregulation of ERK1/2 and connexin43 phosphorylation in vitro. Additionally, pulsatile shear stress significantly suppressed miR-302 expression and exogenously expression of miR-302 cluster inhibited ERK1/2 and connexin43 phosphorylation. Finally, elevated expression of miR-302 cluster not only improved cognitive function of TBI rats but also attenuated brain damage by suppressing edema and reducing contusion volume. Our study suggests that miR-302 protects rats from TBI induced brain damage and cognitive impairment and may represent an effective therapeutic strategy for TBI.

Copyright © 2019. Published by Elsevier B.V.

Language: en

Keywords

ERK1/2; Traumatic brain injury (TBI); cognitive function; connexin43; miR-302 cluster