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LncRNA-AC020978 Promotes Metabolic Reprogramming in M1 Microglial Cells in Postoperative Cognitive Disorder via PKM2
Genghuan Wang1, Jian Shen1, Qiaobing Guan2
1Department of Neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, China.
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.
Insights
Long non-coding RNA AC020978 exacerbates postoperative cognitive disorder (POCD) by promoting microglial M1 polarization and inflammation. Silencing AC020978 alleviates POCD, suggesting it as a therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Postoperative cognitive disorder (POCD) is a common complication after surgery.
- The role of long non-coding RNAs (lncRNAs) in POCD pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the role of lncRNA-AC020978 in the development of POCD.
- To elucidate the underlying molecular mechanisms involving microglial activation and inflammation.
Main Methods:
- Constructed a POCD mouse model using isoflurane anesthesia and abbreviated laparotomy.
- Utilized lentivirus to silence or overexpress AC020978 in vivo and in vitro.
- Assessed cognitive function using the Morris water maze test.
- Analyzed M1 macrophage polarization, inflammatory factors, and protein expression via flow cytometry, ELISA, and Western blotting.
- Examined brain tissue pathology using H&E, Nissl, and immunohistochemical staining.
Main Results:
- AC020978 overexpression aggravated cognitive deficits and promoted M1 polarization of peripheral and central immune cells in POCD mice.
- AC020978 silencing ameliorated cognitive dysfunction and suppressed microglial activation and M1 polarization.
- In vitro, AC020978 promoted microglial M1 polarization and glycolysis by enhancing PKM2 expression and phosphorylation.
- AC020978 interacts with PKM2 to regulate microglial glycolysis and M1 polarization, impacting central inflammation in POCD.
Conclusions:
- lncRNA-AC020978 plays a critical role in promoting POCD progression.
- AC020978 facilitates POCD by enhancing microglial M1 polarization and glycolysis via the PKM2 pathway.
- Targeting AC020978 may offer a novel therapeutic strategy for managing POCD.
