Upregulation of miR-496 Rescues Propofol-induced Neurotoxicity by Targeting Rho Associated Coiled-coil Containing Protein Kinase 2 (ROCK2) in Prefrontal Cortical Neurons

Author(s): Zemei Mao, Wanju Wang, Haixia Gong*, Yinghui Wu, Yang Zhang, Xinlei Wang

Journal Name: Current Neurovascular Research

Volume 17 , Issue 2 , 2020

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Abstract:

Objective: Early exposure to general anesthesia in children might be a potentially highrisk factor for learning and behavioral disorders. The mechanism of neurotoxicity induced by general anesthesia was not defined. miR-496 could regulate cerebral injury, while the roles of miR- 496 in neurotoxicity were not elucidated. Therefore, we aimed to investigate the effects of miR- 496 in neurotoxicity induced by propofol.

Methods: Primary Prefrontal Cortical (PFC) neurons were isolated from neonatal rats and treated with propofol to induce neurotoxicity. Cell viability was detected by (3-(4,5-Dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The target relationship of miR-496 and Rho Associated Coiled-Coil Containing Protein Kinase 2 (ROCK2) was explored using luciferase assays.

Results: Propofol decreased cell viability, promoted cell apoptosis, and decreased the expression of miR-496 in PFC neurons in a dose-dependent manner. Overexpression of miR-496 attenuated neurotoxicity induced by propofol in PFC neurons. ROCK2 was a target of miR-496, and miR-496 oppositely modulated the expression of ROCK2. Besides, propofol increased the expression of ROCK2 through inhibiting miR-496 in PFC neurons. Overexpression of miR-496 attenuated propofol- induced neurotoxicity by targeting ROCK2 in PFC neurons.

Conclusion: miR-496 was decreased in PFC neurons treated with propofol, and overexpression of miR-496 attenuated propofol-induced neurotoxicity by targeting ROCK2. miR-496 and ROCK2 may be promising targets for protecting propofol-induced neurotoxicity.

Keywords: miR-496, ROCK2, propofol, neurotoxicity, viability, apoptosis.

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Article Details

VOLUME: 17
ISSUE: 2
Year: 2020
Page: [188 - 195]
Pages: 8
DOI: 10.2174/1567202617666200506101926
Price: $65

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