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Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy

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Abstract

Temporal lobe epilepsy (TLE) is a complex neurological disease, and its occurrence and development are closely related to the autophagy signaling pathway. However, the mechanism by which electroacupuncture (EA) affects the regulation of autophagy has not been fully elucidated. TLE gene chip dataset GSE27166 and data from rats without epilepsy (n = 6) and rats with epilepsy (n = 6) were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in the TLE and control groups were identified with the online tool GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyse the functional and pathway enrichment of genes in the most important modules. A rat model of TLE induced by lithium–pilocarpine treatment was established. EA treatment at DU20 and DU14 in TLE rats was performed for 2 weeks. Neuronal regeneration was determined using immunofluorescence staining. The protein levels of AKT/mTOR signaling pathway and autophagy markers were detected through western blotting and immunohistochemistry. This study identified 1837 DEGs, including 798 upregulated genes and 1039 downregulated genes. GO enrichment and KEGG analyses were performed on DEGs and revealed functional enrichment mainly in the mTOR signaling pathway and autophagy-animal. Furthermore, the number of mature neurons was significantly increased upon coexpressing BrdU/NeuN in TLE rats treated with EA. Western blotting and immunohistochemistry results showed significantly decreased levels of the phosphorylated-AKT and p-mTOR in the hippocampal CA3 and DG regions of TLE rats with EA treatment. And increased p-ULK1/ULK1, LC3-II/LC3-I and p62 levels in TLE rats with EA stimulation. Therefore, this study suggested that EA promoted autophagy in hippocampal neurons during the onset of epilepsy by regulating the AKT/mTOR signaling pathway to treat epilepsy.

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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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Acknowledgements

This work was supported by grants from the Medical and health science and technology project of Suzhou High-tech Zone (key project) (Grant No. 2018Z002); 2019 Suzhou Livelihood Science and Technology Guidance Project (Grant No. SYSD2019078), Scientific Innovation Fund Project of Suzhou High-tech Zone People’s Hospital (Grant No. SGY2018B01).

Funding

The Medical and health science and technology project of Suzhou High-tech Zone (key project) (2018Z002); 2019 Suzhou Livelihood Science and Technology Guidance Project (SYSD2019078), Scientific Innovation Fund Project of Suzhou High-tech Zone People’s Hospital (SGY2018B01).

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  1. Dongsheng Gao, Linqing Ma and Yunliang Xie have contributed equally in this work.

Authors and Affiliations

  1. The People’s Hospital of Suzhou New District, Suzhou, China

    Dongsheng Gao, Linqing Ma, Yunliang Xie, You Zhou & Xiaoyan Yang

  2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China

    Bo Xiao & Wenbiao Xiao

  3. Department of Neurology, The First Affiliated Hospital of Suzhou University, 899 Pinghai Road, Suzhou, Jiangsu, China

    Shouru Xue & Xiuying Cai

  4. Department of Neurology, The People’s Hospital of Suzhou New District, 95 Huashan Road, Suzhou, Jiangsu, China

    Xiaoyan Yang

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  1. Dongsheng Gao
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  4. Bo Xiao
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Correspondence to Xiuying Cai or Xiaoyan Yang.

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This study was approved by the Ethics Committee of People’s Hospital of Suzhou New District. All animal experiments were carried out in accordance with the Chinese governing law on the use of medical laboratory animal.

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Gao, D., Ma, L., Xie, Y. et al. Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy. Neurochem Res 47, 2396–2404 (2022). https://doi.org/10.1007/s11064-022-03634-9

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  • DOI: https://doi.org/10.1007/s11064-022-03634-9

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