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Effects of Meranzin Hydrate On the LncRNA–miRNA–mRNA Regulatory Network in the Hippocampus of a Rat Model of Depression

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Abstract

Meranzin hydrate (MH) is a frequently used antidepressant drug in China; however it underlying mechanism remains unknown. In this study, we aimed to explore whether MH could ameliorate depression-like behavior in rats by regulating the competitive endogenous RNA (ceRNA) network. We developed a depression-like rat model using an unpredictable chronic mild stress (UCMS) protocol, and the differentially expressed lncRNAs, miRNAs, and mRNAs were identified between the model group and MH group. Then, a ceRNA network responding to MH treatment was constructed by their corresponding relationships in the databases. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to explore molecular mechanisms associated with MH treatment. The study indicated that rats in the model group showed loss of weight and deteriorated behavior in behavior tests compared with rats in the normal group. A total of 826 lncRNAs, 121 miRNAs, and 954 mRNAs were differentially expressed in the hippocampus of UCMS rats after MH treatment. In addition, 13 miRNAs were selected, and 12 of them were validated in the hippocampus by qRT-PCR. Then, we predicted upstream lncRNAs and downstream mRNAs of the validated miRNAs and interacted with the results of microarrays. Eventually, a lncRNA–miRNA–mRNA regulatory network, responding to MH treatment, was constructed based on the 314 lncRNAs, 11 miRNAs, and 221 mRNAs. KEGG pathways suggested that these genes may be highly related to Wnt signaling, axon guidance, and MAPK signaling pathways. All these results suggest that MH may be a potential representative compound for the treatment of depression, and its mechanism of action is related to the ceRNA modification.

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Funding

This project was supported by a grant (No. 81774281 and No. 81303098) from the National Natural Science Foundation of China and partly supported by the Natural Science Foundation of Hunan Province (No. 2019JJ40509).

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Authors and Affiliations

  1. Department of Integrated Traditional Chinese & Western Internal Medicine, The Second Xiangya Hospital, Central South University, Changsha, 410001, Hunan, China

    Kechao Nie

  2. The First Hospital of Hunan University of Chinese Medicine, Changsha, 410021, Hunan, China

    Lin Liu

  3. Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Luqi Peng, Mei Zhang, Chunhu Zhang, Bo Xiao, Zian Xia & Wei Huang

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  1. Kechao Nie
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Contributions

Kechao Nie and Wei Huang designed this study. Luqi Peng, Mei Zhang, Chunhu Zhang, Bo Xiao, and Zian Xia participated in the collecting the samples, carried out the study, and analysis and interpretation of the data. Kechao Nie and Wei Huang aided in review, editing, and revising the manuscript.

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Correspondence to Wei Huang.

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Nie, K., Liu, L., Peng, L. et al. Effects of Meranzin Hydrate On the LncRNA–miRNA–mRNA Regulatory Network in the Hippocampus of a Rat Model of Depression. J Mol Neurosci 72, 910–922 (2022). https://doi.org/10.1007/s12031-022-01971-6

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