Sevoflurane impairs m6A-mediated mRNA translation and leads to fine motor and cognitive deficits

Zhang, Lei; Cheng, Yanyong; Xue, Zhenyu; Li, Jingjie; Wu, Niming; Jia, Yan; Wang, Jie; Wang, Chao; Chen, Weidong; Zhou, Tao; Qiu, Zilong; Jiang, Hong

doi:10.1007/s10565-021-09601-4

Cited by 31 publications

(25 citation statements)

References 41 publications

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“…Nowadays, some researchers tried to focus on the role of RNA methylation modification in neonatal GA induced neurotoxicity. Zhang et al (2021) reported that multiple sevoflurane anesthesia exposures may induce the downregulation of YTHDF1 in the prefrontal cortex of mice which is a critical reader protein of m 6 A RNA methylation reported to promote synthesis of target transcripts in the hippocampus of adult mice and thereby facilitate learning and memory ( Shi et al, 2018 ). As a result, this change of YTHDF1 led to the decrease of m 6 A RNA methylation and protein level of the presynaptic protein synaptophysin and cognitive deficits ( Zhang et al, 2021 ).…”

Section: The Rna Methylationmentioning

confidence: 99%

“… Zhang et al (2021) reported that multiple sevoflurane anesthesia exposures may induce the downregulation of YTHDF1 in the prefrontal cortex of mice which is a critical reader protein of m 6 A RNA methylation reported to promote synthesis of target transcripts in the hippocampus of adult mice and thereby facilitate learning and memory ( Shi et al, 2018 ). As a result, this change of YTHDF1 led to the decrease of m 6 A RNA methylation and protein level of the presynaptic protein synaptophysin and cognitive deficits ( Zhang et al, 2021 ). After this experiment, to further investigate the possible function and effect of m 6 A modification on this sevoflurane-related neurotoxicity, these researchers published an article this year that revealed the changes in the m 6 A methylation profile of the prefrontal cortex of infant rhesus macaques ( Chen et al, 2022 ).…”

Section: The Rna Methylationmentioning

confidence: 99%

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The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia

Yan

Jiao

et al. 2022

Front. Mol. Neurosci.

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It has been widely demonstrated by numerous preclinical studies and clinical trials that the neonates receiving repeated or long-time general anesthesia (GA) could develop prolonged cognitive dysfunction. However, the definite mechanism remains largely unknown. Epigenetics, which is defined as heritable alterations in gene expression that are not a result of alteration of DNA sequence, includes DNA methylation, histone post-translational modifications, non-coding RNAs (ncRNAs), and RNA methylation. In recent years, the role of epigenetic modifications in neonatal GA-induced neurotoxicity has been widely explored and reported. In this review, we discuss and conclude the epigenetic mechanisms involving in the process of neonatal anesthesia-induced cognitive dysfunction. Also, we analyze the wide prospects of epigenetics in this field and its possibility to work as treatment target.

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Section: The Rna Methylationmentioning

confidence: 99%

Section: The Rna Methylationmentioning

confidence: 99%

The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia

Yan

Jiao

et al. 2022

Front. Mol. Neurosci.

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“…Sevoflurane exposure has been shown to induce behavioral deficits, poor memory performance, and neurofunctional abnormalities by disrupting excitatory neurons in the PFC (Xu et al, 2018;Xie et al, 2020;Zhao et al, 2020). Our previous study found that sevoflurane-induced impairment in m6A-mediated mRNA translation in the PFC was related to fine motor deficits (Zhang L. et al, 2021). Sevoflurane exposure contributed to higher tau concentration, lower brain mitochondrial metabolism, aberrant non-coding RNA expression, and hypermethylation in the hippocampus, which result in impairment of neurocognition, neurogenesis, learning, and memory (Hu et al, 2019;Shao and Xia, 2019;Yu et al, 2020;Fan et al, 2021); indeed, the hippocampus is heavily involved in learning, cognition, memory acquisition, and storage (Shao and Xia, 2019).…”

Section: Introductionmentioning

confidence: 97%

“…Various brain regions were included in such studies, especially the striatum, hypothalamus, prefrontal cortex (PFC), and hippocampus (Song et al, 2019;Zhang et al, 2019a;Xie et al, 2020;Yamamoto et al, 2020;Zhao et al, 2020;Zhang L. et al, 2021). The differentially expressed genes (DEGs) identified by transcriptome studies and verified by subsequent experiments have helped to explain the observed adverse effects of sevoflurane.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, a primate model with multiple sevoflurane exposures which used in our previous researches (Zhang et al, 2019a;Cheng et al, 2020;Zhang L. et al, 2021;Chen et al, 2022) to study the mechanism of sevoflurane-induced neurotoxicity was applied. We explored the gene expression profiling in the amygdala and PFC of rhesus macaques (Macaca mulatta), with or without sevoflurane exposure, by RNA-seq to elucidate the previously identified dysregulated genes and pathways related to sevoflurane exposure.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Prefrontal Cortex and Amygdala Expressed Genes Associated With Sevoflurane Anesthesia on Non-human Primate

Cheng

Liu

Zhang

et al. 2022

Front. Integr. Neurosci.

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Clinical trials and animal studies have indicated that long-term use or multiple administrations of anesthesia may lead to fine motor impairment in the developing brain. Most studies on anesthesia-induced neurotoxicity have focused on the hippocampus and prefrontal cortex (PFC); however, the role of other vital encephalic regions, such as the amygdala, is still unclear. Herein, we focused on sevoflurane, the most commonly used volatile anesthetic in infants, and performed a transcriptional analysis of the PFC and amygdala of macaques after multiple exposures to the anesthetic by RNA sequencing. The overall, overlapping, and encephalic region-specific transcriptional patterns were separately analyzed to reveal their functions and differentially expressed gene sets that were influenced by sevoflurane. Specifically, functional, protein–protein interaction, neighbor gene network, and gene set enrichment analyses were performed. Further, we built the basic molecular feature of the amygdala by comparing it to the PFC. In comparison with the amygdala’s changing pattern following sevoflurane exposure, functional annotations of the PFC were more enriched in glial cell-related biological functions than in neuron and synapsis development. Taken together, transcriptional studies and bioinformatics analyses allow for an improved understanding of the primate PFC and amygdala.

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Neurobehavioral effects of general anesthesia and cochlear implantation on hearing‐impaired infants: A prospective observational cohort study

Zhou

et al. 2023

Brain and Behavior

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IntroductionThe potential adverse effects of prolonged exposure to anesthetics in pediatric patients with severe‐to‐profound sensorineural hearing loss remain unclear. This study aimed to examine whether early bilateral cochlear implantation involving long‐duration anesthetic exposure caused greater developmental impairment than that with unilateral cochlear implantation.MethodsThis prospective observational study included normally developing infants with bilateral severe‐to‐profound sensorineural hearing loss aged 6 months to 2 years who were candidates for unilateral/bilateral cochlear implantation surgery. Baseline (T0), 6‐month (T1), and 1‐year (T2) Gesell Scale scores were measured. The outcomes included fine motor, adaptability, gross motor, language, and social skills scale 6 and 12 months postoperatively.ResultThe 90 enrolled children with bilateral severe‐to‐profound sensorineural hearing loss (unilateral n = 43; bilateral n = 47) had a younger bilateral group (11.00 ± 3.66 vs. 15.63 ± 6.99 months, p < .001). Anesthesia duration was longer in the bilateral group (271.57 ± 36.09 vs. 148.81 ± 25.60 min, p < .001). Gross motor, fine motor, adaptability, and language scores improved in both groups, and no significant between‐group differences occurred in the fine motor scale at T1 and T2. Language developmental quotients improved significantly in the bilateral group compared with the unilateral group at T1 (mean differences: 25.07 ± 4.37 vs. 10.88 ± 4.61, p < .001) and T2 (mean differences: 34.98 ± 5.94 vs. 15.28 ± 6.55, p < .001). Stepwise regression revealed that gross motor, adaptability, language, and social skill developmental quotients at T1 were positively correlated with those at T0. Gross motor, fine motor, and social skill developmental quotients at T2 were negatively correlated with age at operation. Language developmental quotients were positively correlated with T0 values (p < .001) and in the bilateral group (p < .001) at T1 and T2.ConclusionsWhen evaluating young children with bilateral severe‐to‐profound sensorineural hearing loss, despite longer exposures to general anesthesia, bilateral cochlear implantations were associated with more improvement in language scores and no differences in other skills compared with those with only unilateral implantation.

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Sevoflurane impairs m6A-mediated mRNA translation and leads to fine motor and cognitive deficits

Cited by 31 publications

References 41 publications

The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia

The Role of Epigenetic Modifications in Neurotoxicity Induced by Neonatal General Anesthesia

Identification of Prefrontal Cortex and Amygdala Expressed Genes Associated With Sevoflurane Anesthesia on Non-human Primate

Neurobehavioral effects of general anesthesia and cochlear implantation on hearing‐impaired infants: A prospective observational cohort study

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