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

[ Vol. 17 , Issue. 2 ]

Author(s):

Zemei Mao, Wanju Wang, Haixia Gong*, Yinghui Wu, Yang Zhang and Xinlei Wang   Pages 188 - 195 ( 8 )

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.

Affiliation:

Department of Anesthesiology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan City, Hubei Province, 430016, Department of General Surgery, Hubei Provincial Hospital of Integrated Chinese & Western Medicine, Wuhan City, Hubei Province, 430015, Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, Department of Anesthesiology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan City, Hubei Province, 430016, Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006, Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, 330006



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