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LncRNA Rian ameliorates sevoflurane anesthesia-induced cognitive dysfunction through regulation of miR-143-3p/LIMK1 axis.

Abstract
Sevoflurane could stimulate neurotoxicity and result in postoperative cognitive dysfunction (POCD). Long non-coding RNAs (lncRNAs) have been implicated in the regulation of nervous system disease. This study was performed to investigate role and mechanism of lncRNA Rian (RNA imprinted and accumulated in nucleus) in sevoflurane anesthesia-induced cognitive dysfunction. Mice post-sevoflurane anesthesia showed cognitive impairments and neuronal damage and apoptosis. However, intracerebroventricularly injection with Adenovirus (Ad) for the over-expression of Rian ameliorated sevoflurane-induced neuronal damage and apoptosis. Cognitive impairments induced by sevoflurane were attenuated by injection with Ad-Rian. Moreover, transfection with Ad-Rian also protected isolated primary hippocampal neurons against sevoflurane-induced decrease of cell viability and increase of lactic acid dehydrogenase (LDH) and apoptosis. Mechanistically, Rian bind to miR-143-3p, and decreased expression of LIMK1 (Lim kinase 1) through negative regulation of miR-143-3p. Knockdown of LIMK1 aggravated sevoflurane-induced decrease of cell viability and increase of LDH and apoptosis in neurons, while over-expression attenuated LIMK1 silence-induced neuronal damage post-sevoflurane anesthesia. In conclusion, Rian demonstrated neuroprotective effects against sevoflurane anesthesia-induced cognitive dysfunction through regulation of miR-143-3p/LIMK1 axis, providing promising target for sevoflurane anesthesia-induced cognitive dysfunction.
AuthorsYang Yu, Wei Zhang, Dengyan Zhu, Haitao Wang, Hua Shao, Yue Zhang
JournalHuman cell (Hum Cell) Vol. 34 Issue 3 Pg. 808-818 (May 2021) ISSN: 1749-0774 [Electronic] Japan
PMID33616869 (Publication Type: Journal Article)
Chemical References
  • Anesthetics, Inhalation
  • MIRN143 microRNA, human
  • MicroRNAs
  • Neuroprotective Agents
  • Nuclear Proteins
  • Rian protein, mouse
  • Sevoflurane
  • L-Lactate Dehydrogenase
  • Lim Kinases
  • Limk1 protein, mouse
Topics
  • Anesthetics, Inhalation (adverse effects)
  • Animals
  • Apoptosis (drug effects, genetics)
  • Cell Survival (drug effects, genetics)
  • Gene Expression (drug effects, genetics)
  • Hippocampus (cytology)
  • L-Lactate Dehydrogenase (metabolism)
  • Lim Kinases (genetics, metabolism)
  • Mice
  • MicroRNAs (genetics, metabolism)
  • Neurons (metabolism, physiology)
  • Neuroprotective Agents
  • Nuclear Proteins (administration & dosage, pharmacology, physiology)
  • Postoperative Cognitive Complications (chemically induced, drug therapy, genetics)
  • Sevoflurane (adverse effects)

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