Whole transcriptome sequencing reveals dexmedetomidine-improves postoperative cognitive dysfunction in rats via modulating lncRNA

Deng, Fumou; Cai, Lily; Zhou, Bin; Zhou, Zhidong; Xu, GuoHai

doi:10.1007/s13205-020-02190-9

Original Article
Published: 13 April 2020

Whole transcriptome sequencing reveals dexmedetomidine-improves postoperative cognitive dysfunction in rats via modulating lncRNA

Fumou Deng¹,
Lily Cai²,
Bin Zhou¹,
Zhidong Zhou¹ &
GuoHai Xu¹

3 Biotech volume 10, Article number: 202 (2020) Cite this article

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Abstract

The aim of this study was to explore the underlying mechanism and function of dexmedetomidine (Dex)-regulated long non-coding RNAs (lncRNAs) in improving postoperative cognitive dysfunction (POCD) in rats. The established POCD model, Dex treatment model in rats, Morris water maze testing, and HE staining assays were used to evaluate the efficacy of Dex in POCD treatment in rats. Hippocampus samples of rats from the POCD group and the Dex group were used for lncRNA sequencing. The expression of five differentially expressed lncRNAs (DElncRNAs) was verified by quantitative reverse transcription PCR (qRT-PCR). Competing endogenous RNAs (ceRNA) network was constructed using Cytoscape. The concentration of inflammatory cytokines were measured by ELISA. Microglia proliferation and apoptosis were assessed using CCK-8 assay and flow cytometry, respectively. In the Dex group, the escape latency was shorter, neuron cell injury levels were alleviated, and the expression levels of TNF-α and IL-1β were significantly down-regulated compared with the POCD group. A total of 60 DE lncRNAs were identified, including 16 up- and 44 down-regulated lncRNAs in the Dex group. KEGG pathway analysis revealed that DElncRNAs were significantly enriched in cytokine–cytokine receptor interactions, the p53 signaling pathway, and the NF-kappa B signaling pathway. The qRT-PCR results and ceRNA network suggested that the lncRNA LOC102546895 may play a key role in POCD. LOC102546895 inhibited proliferation while promoting apoptosis in microglial cells and promoted the mRNA and protein expression of the target gene Npas4. Our findings showed that Dex alleviated POCD in rats and regulated lncRNAs expression profile in the hippocampus tissues of rats with POCD. In conclusion, our study outcome proposes that Dex-regulated lncRNA LOC102546895 may play a role in rats with POCD through targeting Npas4.

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Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Affiliations

Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang, Jiangxi, China
Fumou Deng, Bin Zhou, Zhidong Zhou & GuoHai Xu
Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
Lily Cai

Authors

Fumou Deng
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Lily Cai
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Bin Zhou
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Zhidong Zhou
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GuoHai Xu
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Contributions

Conceptualization: ZZ and GX. Data curation: ZZ and GX. Formal analysis: FD and LC. Funding acquisition: ZZ and GX. Investigation: FD, LC and BZ. Methodology: FD, LC and BZ. Software: FD. Writing—original draft: FD and LC. Writing—review and editing: FD, LC and BZ. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zhidong Zhou or GuoHai Xu.

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Conflict of interest

The authors declare that there are no conflicts of interest.

Ethics approval and consent to participate

All rat experiments completely adhered to the Guide for the Care and Use of Laboratory Animals (National Institutes of Health). All the experiments were approved by the Institutional Animal Care and Use Committee of the second affiliated hospital of Nanchang university.

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Supplementary file1 (PDF 157 kb)

Supplementary file2 (PDF 85 kb)

Supplementary file3 (PDF 83 kb)

Supplement Table 4.

The specific information detailing DE lncRNAs (XLSX 15 kb)

Supplement Table 5.

The specific information detailing DE mRNAs (XLSX 57 kb)

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Deng, F., Cai, L., Zhou, B. et al. Whole transcriptome sequencing reveals dexmedetomidine-improves postoperative cognitive dysfunction in rats via modulating lncRNA. 3 Biotech 10, 202 (2020). https://doi.org/10.1007/s13205-020-02190-9

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Received: 19 January 2020
Accepted: 01 April 2020
Published: 13 April 2020
DOI: https://doi.org/10.1007/s13205-020-02190-9

Keywords

Postoperative cognitive dysfunction
Dexmedetomidine
lncRNA LOC102546895
RNA sequencing