Transcriptomic analysis reveals the molecular mechanism of Alzheimer‐related neuropathology induced by sevoflurane in mice

Ge, Xing; Zhang, Ying; Zuo, Yong; Israr, Muhammad; Li, Bowen; Yu, Peng; Gao, Guofen; Chang, Yan‐Zhong; Shi, Zhenhua

doi:10.1002/jcb.29020

Cited by 14 publications

(15 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These unbiased assays suggest that many genes and molecular networks might be involved in sevoflurane-induced developmental neurotoxicity. In particular, three (MeCP2, Ctla2a, and Jun) of these dysregulated mRNAs have already been indicated as being associated with sevoflurane-induced neurotoxicity in previous studies [29][30][31][32].…”

Section: Discussionmentioning

confidence: 85%

Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways

Jiang

Arzua

Yan

et al. 2021

IJMS

View full text Add to dashboard Cite

Sevoflurane, one of the most commonly used pediatric anesthetics, was found to cause developmental neurotoxicity. To understand specific risk groups and develop countermeasures, a better understanding of its mechanisms is needed. We hypothesize that, as in many other brain degeneration pathways, long non-coding RNAs (lncRNAs) are involved in the sevoflurane-induced neurotoxicity. Postnatal day 7 (PD7) mice were exposed to 3% sevoflurane for 6 h. To quantify neurotoxicity in these mice, we (1) detected neural apoptosis through analysis of caspase 3 expression level and activity and (2) assessed long-term learning ability via the Morris water maze at PD60. To elucidate specific mechanisms, profiles of 27,427 lncRNAs and 18,855 messenger RNAs (mRNAs) in mouse hippocampi were analyzed using microarray assays. Sevoflurane-induced abnormal lncRNA and mRNA expression-associated function pathways were predicted by bioinformatic analysis. We found that sevoflurane induced significant neurotoxicity, causing acute neuroapoptosis and abnormal expression of 148 mRNAs and 301 lncRNAs on PD7 in mouse hippocampus. Additionally, exposed mice exhibited impaired memory on PD60. Bioinformatic analysis predicted that the dysregulated mRNAs, which are highly correlated with their co-expressed dysregulated lncRNAs, might be involved in 34 neurodegenerative signaling pathways (e.g., brain cell apoptosis and intellectual developmental disorder). Our study reveals for the first time that neonatal exposure to 3% sevoflurane induces abnormal lncRNA and mRNA expression profiles. These dysregulated lncRNAs/mRNAs form wide molecular networks that might contribute to various functional neurological disease pathways in the hippocampus, resulting in the observed acute apoptosis and impaired long-term memory.

show abstract

Section: Discussionmentioning

confidence: 85%

Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways

Jiang

Arzua

Yan

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…MiRNA322 (paired with protogenin Prtg) is associated with apoptosis and Alzheimer's disease (AD) [67]. Finally, Mir100 (paired with cadherin Cdh9), is associated with neurological disorders such as AD, schizophrenia and autism [68][69][70][71].…”

Section: Discussionmentioning

confidence: 99%

Combining feature selection and shape analysis uncovers precise rules for miRNA regulation in Huntington’s disease mice

et al. 2020

View full text Add to dashboard Cite

Background: MicroRNA (miRNA) regulation is associated with several diseases, including neurodegenerative diseases. Several approaches can be used for modeling miRNA regulation. However, their precision may be limited for analyzing multidimensional data. Here, we addressed this question by integrating shape analysis and feature selection into miRAMINT, a methodology that we used for analyzing multidimensional RNA-seq and proteomic data from a knock-in mouse model (Hdh mice) of Huntington's disease (HD), a disease caused by CAG repeat expansion in huntingtin (htt). This dataset covers 6 CAG repeat alleles and 3 age points in the striatum and cortex of Hdh mice. Results: Remarkably, compared to previous analyzes of this multidimensional dataset, the miRAMINT approach retained only 31 explanatory striatal miRNA-mRNA pairs that are precisely associated with the shape of CAG repeat dependence over time, among which 5 pairs with a strong change of target expression levels. Several of these pairs were previously associated with neuronal homeostasis or HD pathogenesis, or both. Such miRNA-mRNA pairs were not detected in cortex. Conclusions: These data suggest that miRNA regulation has a limited global role in HD while providing accuratelyselected miRNA-target pairs to study how the brain may compute molecular responses to HD over time. These data also provide a methodological framework for researchers to explore how shape analysis can enhance multidimensional data analytics in biology and disease.

show abstract

“…(paired with cadherin Cdh9), is associated with neurological disorders such as AD, schizophrenia and autism [68][69][70][71].…”

Section: Discussionmentioning

confidence: 99%

Combining feature selection and shape analysis uncovers precise rules for miRNA regulation in Huntington’s disease mice

Mégret

Nair

Dancourt

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundMicroRNA (miRNA) regulation is associated with several diseases, including neurodegenerative diseases. Several approaches can be used for modeling miRNA regulation. However, their precision may be limited for analyzing multidimensional data. Here, we addressed this question by integrating shape analysis and feature selection into miRAMINT, a methodology that we used for analyzing multidimensional RNA-seq and proteomic data from a knock-in mouse model (Hdh mice) of Huntington's disease (HD), a disease caused by CAG repeat expansion in huntingtin (htt).This dataset covers 6 CAG repeat alleles and 3 age points in the striatum and cortex of Hdh mice. ResultsRemarkably, compared to previous analyzes of this multidimensional dataset, the miRAMINT approach retained only 31 explanatory striatal miRNA-mRNA pairs that are precisely associated with the shape of CAG repeat dependence over time, among which 5 pairs with a strong change of target expression levels. Several of these pairs were previously associated with neuronal homeostasis or HD pathogenesis, or both. Such miRNA-mRNA pairs were not detected in cortex. ConclusionsThese data suggest that miRNA regulation has a limited global role in HD while providing accurately-selected miRNA-target pairs to study how the brain may compute molecular responses to HD over time. These data also provide a methodological framework for researchers to explore how shape analysis can enhance multidimensional data analytics in biology and disease.2

show abstract

Transcriptomic analysis reveals the molecular mechanism of Alzheimer‐related neuropathology induced by sevoflurane in mice

Cited by 14 publications

References 40 publications

Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways

Expression Signature of lncRNAs and mRNAs in Sevoflurane-Induced Mouse Brain Injury: Implication of Involvement of Wide Molecular Networks and Pathways

Combining feature selection and shape analysis uncovers precise rules for miRNA regulation in Huntington’s disease mice

Combining feature selection and shape analysis uncovers precise rules for miRNA regulation in Huntington’s disease mice

Contact Info

Product

Resources

About