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mRNA and Long Non-coding RNA Expression Profiles in Rats Reveal Inflammatory Features in Sepsis-Associated Encephalopathy

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Abstract

Sepsis-associated encephalopathy (SAE) is related to cognitive sequelae in patients in the intensive care unit and can have serious impacts on quality of life after recovery. Although various pathogenic pathways are involved in SAE development, little is known concerning the global role of long non-coding RNAs (lncRNAs) in SAE. Herein, we employed transcriptome sequencing approaches to characterize the effects of lipopolysaccharide (LPS) on lncRNA expression patterns in brain tissue isolated from Sprague–Dawley rats with and without SAE. We performed high-throughput transcriptome sequencing after LPS was intraperitoneally injected and predicted targets and functions using bioinformatics tools. Subsequently, we explored the results in detail according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. LncRNAs were differentially expressed in brain tissue after LPS treatment. After 6 h of LPS exposure, expression of 400 lncRNAs were significantly changed, including an increase in 316 lncRNAs and a decrease in 84 lncRNAs. In addition, 155 mRNAs were differentially expressed, with 84 up-regulated and 71 down-regulated. At 24 h post-treatment, expression of 117 lncRNAs and 57 mRNAs was consistently elevated, while expression of 79 lncRNAs and 21 mRNAs was decreased (change >1.5-fold; p <0.05). We demonstrated for the first time that differentially expressed lncRNAs were predicted to be enriched in a post-chaperonin tubulin folding pathway (GO: 007023), which is closely related to the key step in the tubulin folding process. Interestingly, the predicted pathway (KEGG 04360: axon guidance) was significantly changed under the same conditions. These results reveal that LPS might influence the construction and polarization of microtubules, which exert predominant roles in synaptogenesis and related biofunctions in the rodent central nervous system (CNS). An inventory of LPS-modulated expression profiles from the rodent CNS is an important step toward understanding the function of mRNAs, including lncRNAs, and suggests that microtubule malformation and dysfunction may be involved in SAE pathogenesis.

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Abbreviations

CLP:

Caecal ligation and puncture

CNS:

Central nervous system

FDR:

False discovery rate

GO:

Gene Ontology

ICU:

Intensive care unit

KEGG:

Kyoto encyclopedia of genes and genomes

LPS:

Lipopolysaccharide

lncRNAs:

Long non-coding RNAs

NT:

Nucleotides

RPKM:

Reads per kilobase per million mapped reads

SAE:

Sepsis-associated encephalopathy

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Funding

Funding for this project was provided by the Natural Science Foundation of China (Grant Number: 81071530).

Author Contributions

WS was a major contributor in manuscript writing and data analysis. LP gave an important direction for study design. ZL participated in animal care and RNA extraction. All authors read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital, China Medical University, 155 North Nanjing Street, Shenyang, 110001, Liaoning, China

    WenChong Sun, Ling Pei & Zuodi Liang

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  1. WenChong Sun
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  2. Ling Pei
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  3. Zuodi Liang
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Correspondence to Ling Pei.

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Sun, W., Pei, L. & Liang, Z. mRNA and Long Non-coding RNA Expression Profiles in Rats Reveal Inflammatory Features in Sepsis-Associated Encephalopathy. Neurochem Res 42, 3199–3219 (2017). https://doi.org/10.1007/s11064-017-2357-y

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