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Helicid Alleviates Neuronal Apoptosis of Rats with Depression-Like Behaviors by Downregulating lncRNA-NONRATT030918.2

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Abstract

Helicid (HEL) has been found to possess antidepressant pharmacological activity. The paper was to testify to the precise molecular mechanism through which HEL regulates lncRNA-NONRATT030918.2 to exert an antidepressant impression in depression models. A depression model stimulated using chronic unpredictable mild stress (CUMS) was created in rats, and the depressive state of the rats was assessed through behavioral experiments. Additionally, an in vitro model of PC12 cells induced by corticosterone (CORT) was established, and cytoactive was tested using the CCK8. The subcellular localization of the NONRATT030918.2 molecule was confirmed through a fluorescence in situ hybridization experiment. The relationship between NONRATT030918.2, miRNA-128-3p, and Prim1 was analyzed using dual-luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation assay, and RNA pull-down assay. The levels of NONRATT030918.2, miRNA-128-3p, and Prim1 were tested using Q-PCR. Furthermore, the levels of Prim1, Bax, Bcl-2, and caspase3 were checked through Western blot. The HEL can alleviate the depression-like behavior of CUMS rats (P < 0.05), and reduce the mortality of hippocampal via downregulating the level of NONRATT030918.2 (P < 0.05). In CORT-induced PC12 cells, intervention with HEL led to decreased expression of NONRATT030918.2 and Prim1 (P < 0.05), as well as increased expression of miRNA-128-3p (P < 0.05). This suggests that HEL regulates the expression of NONRATT030918.2 to upregulate miRNA-128-3p (P < 0.05), which in turn inhibits CORT-induced apoptosis in PC12 cells by targeting Prim1 (P < 0.05). The NONRATT030918.2/miRNA-128-3p/Prim1 axis could potentially serve as a crucial regulatory network for HEL to exert its neuroprotective effects.

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Data Availability

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

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Funding

This research was funded by the Introduced Talents Special Science Foundation of Yijishan Hospital of Wannan Medical College (grant no. YR202113), the Key Natural Science Research Project of Anhui Provincial Department of Education (grant no. KJ2021A0858), the Scientific Research Foundation for Middle-aged and Young of Yijishan Hospital of Wannan Medical College (grant no. WK2022F12), Wuhu Science and Technology Project in 2022 (grant no. 2022jc55), 2022 Anhui Health Research Key Project (grant no. AHWJ2022a027), and Research Funds of Center for Xin’an Medicine and Modernization of Traditional Chinese Medicine of IHM (grant no. 2023CXMMTCM007).

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Authors and Affiliations

  1. The First Affiliated Hospital of Wannan Medical College, Yijishan Hospital, Wuhu, 241001, Anhui, China

    Yuan Zhang, Zhen-Yi Jiang, Mei Wang, Xiao-Tong Zhang, Peng Ge & Jiu-Cui Tong

  2. Wannan Medical College, Wuhu, 241002, Anhui, China

    Yuan Zhang, Zhen-Yi Jiang, Mei Wang, Peng Ge, Wei Wang, Yuan-Xiang Zhang & Jiu-Cui Tong

  3. The Second People’s Hospital of Lu’an City, Lu’an, 237008, Anhui, China

    Yuan Zhang

  4. Anhui Provincial Engineering Laboratory for Screening and Re-Evaluation of Active Compounds of Herbal Medicines, Southern Anhui, Wuhu, 241002, Anhui, China

    Jiu-Cui Tong

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Funding acquisition, Jiu-Cui Tong, Yuan-Xiang Zhang, and Xiao-Tong Zhang; methodology, Yuan Zhang, and Zhen-Yi Jiang; resources, Mei Wang; validation, Yuan Zhang, Peng Ge, and Wei Wang; visualization, Zhen-Yi Jiang; writing—original draft, Yuan Zhang. All authors read and approved the final manuscript.

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Correspondence to Yuan-Xiang Zhang or Jiu-Cui Tong.

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The study was approved by the local ethics committee of First Affiliated Hospital of Wannan Medical College (Wuhu, Anhui, China; animal ethics code: WNMC-RATS-2022067; 07 September 2022). All methods were performed in accordance with the relevant guidelines and regulations. The experiments performed in this study also comply with the ARRIVE guidelines 2.0 (https://arriveguidelines.org/).

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Zhang, Y., Jiang, ZY., Wang, M. et al. Helicid Alleviates Neuronal Apoptosis of Rats with Depression-Like Behaviors by Downregulating lncRNA-NONRATT030918.2. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-04192-7

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