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LncRNA-AC020978 Promotes Metabolic Reprogramming in M1 Microglial Cells in Postoperative Cognitive Disorder via PKM2

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Abstract

The present work aimed to explore the role of long non-coding RNA (lncRNA)-AC020978 in postoperative cognitive disorder (POCD) and the underlying mechanism. The POCD mouse model was constructed through isoflurane anesthesia + abbreviated laparotomy. The AC020978 expression in brain tissue was silenced after lentivirus injection, then Morris water maze test was conducted to detect the cognitive disorder level, flow cytometry was performed to analyze M1 macrophage level, ELISA was carried out to measure inflammatory factor levels, H&E, Nissl and immunohistochemical staining was performed to detect the pathological changes in brain tissue, and Western blotting assay was adopted to detect protein expression. In addition, microglial cells were cultured in vitro, after lentivirus infection, the effect of AC020978 on the M1 polarization of microglial cells and glycolysis was observed. AC020978 overexpression promoted POCD progression and aggravated cognitive disorder in mice; in addition, the proportion of peripheral and central M1 cells increased, the inflammatory factor levels were upregulated, and microglial cells were activated. By contrast, AC020978 silencing led to cognitive disorder in mice and suppressed microglial cell activation and M1 polarization. In vitro experimental results indicated that AC020978 promoted the expression and phosphorylation of PKM2, which promoted inflammatory response through enhancing microglial cell glycolysis and M1 polarization. AC020978 interacts with PKM2 to promote the glycolysis and M1 polarization of microglial cells, thus regulating cognitive disorder and central inflammation in POCD.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

I need to thank my colleagues and friends for their help and support in the research, Thanks for the support of the Science and technology planning project of JiaXing.

Funding

The Science and technology planning project of JiaXing [2023AZ11001].

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Author notes

  1. Genghuan Wang and Jian Shen are co-first authors.

Authors and Affiliations

  1. Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China

    Genghuan Wang, Jian Shen & Yingcong Lin

  2. Department of Neurology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China

    Qiaobing Guan, Liping Zhai & Heping Shen

  3. Zhejiang Chinese Medical University, Hangzhou, China

    Yingcong Lin

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  1. Genghuan Wang
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  2. Jian Shen
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Contributions

Genghuan Wang and Jian Shen are responsible for the experiment and acquisition of relevant data; Qiaobing Guan and Yingcong Lin are responsible for paper writing; Liping Zhai and Heping Shen are responsible for project development, financial support.

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Correspondence to Liping Zhai or Heping Shen.

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Wang, G., Shen, J., Guan, Q. et al. LncRNA-AC020978 Promotes Metabolic Reprogramming in M1 Microglial Cells in Postoperative Cognitive Disorder via PKM2. Mol Neurobiol 61, 2459–2467 (2024). https://doi.org/10.1007/s12035-023-03729-6

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  • DOI: https://doi.org/10.1007/s12035-023-03729-6

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