open access

Vol 59, No 2 (2021)
Original paper
Submitted: 2020-11-02
Accepted: 2021-04-27
Published online: 2021-05-18
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Repeated isoflurane exposures of neonatal rats contribute to cognitive dysfunction in juvenile animals: the role of miR-497 in isoflurane-induced neurotoxicity

Yuanyuan Que1, Fangxiang Zhang1, Jing Peng1, Zhuhua Zhang1, Duwen Zhang1, Minghai He1
DOI: 10.5603/FHC.a2021.0011
·
Folia Histochem Cytobiol 2021;59(2):114-123.
Affiliations
  1. Department of Anesthesiology, Guizhou Provincial People’s Hospital, China

open access

Vol 59, No 2 (2021)
ORIGINAL PAPERS
Submitted: 2020-11-02
Accepted: 2021-04-27
Published online: 2021-05-18

Abstract

Introduction. Isoflurane anesthesia at the period of brain development can lead to neurotoxicity and long-term cognitive impairment. This study aimed to investigate the role of miR-497 on isoflurane-induced neurotoxicity. Material and methods. Neonatal rats (P7) were subject to isoflurane for 2 h at P7, P9, and P11. MiR-497 and neuron apoptosis were evaluated in hippocampal tissue by qRT-PCR and western blot. Fear conditioning test and Morris water maze were performed to determine cognitive function. The cell viability of isolated hippocampal neuronal cells exposed to isoflurane was measured using MTT test. The regulation of phospholipase D1 (PLD1) by miR-497 in isolated hippocampal neuronal cells was evaluated by luciferase reporter assays and western blot. Immunohistochemistry and TUNEL staining were employed to examine the PLD1 expression and neuronal cell apoptosis in hippocampus of neonatal rats, respectively. Results. Repeated isoflurane anesthesia led to neurons’ apoptosis and long-term cognitive impairment. Isoflurane exposure led to apoptosis and viability reduction in hippocampal neuronal cells. MiR-497 was observed to be upregulated after isoflurane exposure both in vivo and in vitro. Knockdown of miR-497 attenuated isoflurane-induced neuronal cells apoptosis and viability reduction. Furthermore, PLD1 was predicted and then validated as a novel target of miR-497. miR-497 could negatively regulate PLD1 by binding to its 3’-untranslated region. Downregulation of PLD1 was also observed after isoflurane exposure in neonatal rat hippocampus and hippocampal primary neuronal cell cultures. Conclusions. Induction of miR-497 was involved in isoflurane anesthesia-induced cognitive impairment and neuronal cell apoptosis by targeting PLD1. miR-497 may be a novel potential mechanism in isoflurane-induced neurotoxicity so that our findings provide new insight into a better and understanding of the clinical application of isoflurane.

Abstract

Introduction. Isoflurane anesthesia at the period of brain development can lead to neurotoxicity and long-term cognitive impairment. This study aimed to investigate the role of miR-497 on isoflurane-induced neurotoxicity. Material and methods. Neonatal rats (P7) were subject to isoflurane for 2 h at P7, P9, and P11. MiR-497 and neuron apoptosis were evaluated in hippocampal tissue by qRT-PCR and western blot. Fear conditioning test and Morris water maze were performed to determine cognitive function. The cell viability of isolated hippocampal neuronal cells exposed to isoflurane was measured using MTT test. The regulation of phospholipase D1 (PLD1) by miR-497 in isolated hippocampal neuronal cells was evaluated by luciferase reporter assays and western blot. Immunohistochemistry and TUNEL staining were employed to examine the PLD1 expression and neuronal cell apoptosis in hippocampus of neonatal rats, respectively. Results. Repeated isoflurane anesthesia led to neurons’ apoptosis and long-term cognitive impairment. Isoflurane exposure led to apoptosis and viability reduction in hippocampal neuronal cells. MiR-497 was observed to be upregulated after isoflurane exposure both in vivo and in vitro. Knockdown of miR-497 attenuated isoflurane-induced neuronal cells apoptosis and viability reduction. Furthermore, PLD1 was predicted and then validated as a novel target of miR-497. miR-497 could negatively regulate PLD1 by binding to its 3’-untranslated region. Downregulation of PLD1 was also observed after isoflurane exposure in neonatal rat hippocampus and hippocampal primary neuronal cell cultures. Conclusions. Induction of miR-497 was involved in isoflurane anesthesia-induced cognitive impairment and neuronal cell apoptosis by targeting PLD1. miR-497 may be a novel potential mechanism in isoflurane-induced neurotoxicity so that our findings provide new insight into a better and understanding of the clinical application of isoflurane.

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Keywords

isoflurane; neurotoxicity; rat pups; hippocampal neurons; miR-497; phospholipase D1; cognitive impairment; qPCR; western blot

About this article
Title

Repeated isoflurane exposures of neonatal rats contribute to cognitive dysfunction in juvenile animals: the role of miR-497 in isoflurane-induced neurotoxicity

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 59, No 2 (2021)

Article type

Original paper

Pages

114-123

Published online

2021-05-18

DOI

10.5603/FHC.a2021.0011

Bibliographic record

Folia Histochem Cytobiol 2021;59(2):114-123.

Keywords

isoflurane
neurotoxicity
rat pups
hippocampal neurons
miR-497
phospholipase D1
cognitive impairment
qPCR
western blot

Authors

Yuanyuan Que
Fangxiang Zhang
Jing Peng
Zhuhua Zhang
Duwen Zhang
Minghai He

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