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Mir155hg Accelerates Hippocampal Neuron Injury in Convulsive Status Epilepticus by Inhibiting Microglial Phagocytosis

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Abstract

Convulsive status epilepticus (CSE) is a common critical neurological condition that can lead to irreversible hippocampal neuron damage and cognitive dysfunction. Multiple studies have demonstrated the critical roles that long non-coding RNA Mir155hg plays in a variety of diseases. However, less is known about the function and mechanism of Mir155hg in CSE. Here we investigate and elucidate the mechanism underlying the contribution of Mir155hg to CSE-induced hippocampal neuron injury. By applying high-throughput sequencing, we examined the expression of differentially expressed genes in normal and CSE rats. Subsequent RT-qPCR enabled us to measure the level of Mir155hg in rat hippocampal tissue. Targeted knockdown of Mir155hg was achieved by the AAV9 virus. Additionally, we utilized HE and Tunel staining to evaluate neuronal injury. Immunofluorescence (IF), Golgi staining, and brain path clamping were also used to detect the synaptic plasticity of hippocampal neurons. Finally, through IF staining and Sholl analysis, we assessed the degree of microglial phagocytic function. It was found that the expression of Mir155hg was elevated in CSE rats. HE and Tunel staining results showed that Mir155hg knockdown suppressed the hippocampal neuron loss and apoptosis followed CSE. IF, Golgi staining and brain path clamp data found that Mir155hg knockdown enhanced neuronal synaptic plasticity. The results from IF staining and Sholl analysis showed that Mir155hg knockdown enhanced microglial phagocytosis. Our findings suggest that Mir155hg promotes CSE-induced hippocampal neuron injury by inhibiting microglial phagocytosis.

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Data Availability

All datasets generated in this study were included in the manuscript. The authors supported the original data in this manuscript will be available to any qualified researcher without undue reservation.

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Funding

This research was funded by the National Natural Science Foundation of China (Grant numbers 81971209 and 82101518).

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Author notes

  1. Ming Wang and Binyuan Xu contributed equally to this paper.

Authors and Affiliations

  1. Department of Neurology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Ming Wang, Binyuan Xu & Yinghui Chen

  2. Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China

    Yangmei Xie & Ge Yao

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  1. Ming Wang
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Contributions

Conceived and designed the experiments: WM, CYH and YG. Analyzed the data: WM and XBY. Performed the experiments: WM, XBY, and XYM. Wrote the manuscript: WM and XBY. All authors contributed to this paper and have approved its contents.

Corresponding authors

Correspondence to Ge Yao or Yinghui Chen.

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The authors declare no competing interests.

Ethical Approval

All animal experiments were operated according with protocols and guidelines approved by the Chinese Academy of Sciences Animal Experiment Guide. The animal experiments were approved by the Ethics Committee of Shanghai public health center of Fudan University (Certificate No. 20141601).

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Wang, M., Xu, B., Xie, Y. et al. Mir155hg Accelerates Hippocampal Neuron Injury in Convulsive Status Epilepticus by Inhibiting Microglial Phagocytosis. Neurochem Res (2024). https://doi.org/10.1007/s11064-024-04131-x

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