Related Experiment Video
Updated: Apr 4, 2026
A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018
RUVBL2 Regulates Microglia Metabolic Reprogramming to Mediate Stress Granules Aggregation Exacerbating Postoperative
Lin Zhang1,2,3,4, Zixuan Wang1, Chenyi Yang2,3
1The Third Central Clinical College of Tianjin Medical University, Tianjin, China.
Abstract:
Postoperative delirium (POD) accelerates the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in elderly patients. Microglial metabolic reprogramming, a pivotal aspect of the immune-inflammatory response, modulates microglia-neuron interactions and postoperative cognitive function through microenvironmental alterations. Aberrant overexpression of RUVBL2 disrupts metabolic homeostasis, leading to stress granule (SG) aggregation and fibrosis. This study investigated the role of RUVBL2 in regulating metabolic reprogramming to mediate SG formation, with the aim of identifying novel prognostic targets for inhibiting glycolysis and mitigating POD-induced MCI progression. A POD model was established in aged MCI rats using 3% sevoflurane anesthesia for 3 h, combined with open reduction and internal fixation (ORIF). Multimodal magnetic resonance imaging (MRI) was employed to assess postoperative cognitive function. Glycolytic and oxidative phosphorylation (OXPHOS) activities in primary hippocampal microglia were quantified by extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Lentiviral-mediated RUVBL2 expression modulation was performed to verify its role in microglial metabolic reprogramming. Postoperative hippocampal microglia underwent metabolic reprogramming from OXPHOS to glycolysis, with RUVBL2 expression correlating positively with POD progression. Elevated RUVBL2 expression drove metabolic reprogramming, while RUVBL2 knockdown inhibited this process, alleviated pro-inflammatory microglia-induced neuroinflammation and SG aggregation, and improved spontaneous neural activity and hippocampus-dependent cognitive deficits. In primary hippocampal microglia, RUVBL2 knockdown enhanced OXPHOS-related OCR and reduced glycolysis-associated ECAR, producing a synergistic neuroprotective effect. These findings reveal the critical role of RUVBL2 in regulating POD, highlight metabolic reprogramming as a novel therapeutic target, and suggest RUVBL2 as a promising intervention strategy for POD.
Insights
Postoperative delirium (POD) accelerates cognitive decline. RUVBL2 promotes microglial metabolic reprogramming, worsening POD. Inhibiting RUVBL2 may offer a new therapeutic strategy for POD and Alzheimer's disease progression.
Area of Science:
- Neuroscience
- Immunology
- Metabolic Research
Background:
- Postoperative delirium (POD) exacerbates mild cognitive impairment (MCI) to Alzheimer's disease (AD) transition in elderly patients.
- Microglial metabolic reprogramming is crucial in neuroinflammation and cognitive function post-surgery.
- RUVBL2 overexpression disrupts metabolic balance, causing stress granule (SG) aggregation and fibrosis.
Purpose of the Study:
- Investigate RUVBL2's role in microglial metabolic reprogramming and SG formation.
- Identify RUVBL2 as a prognostic target to inhibit glycolysis and mitigate POD-induced MCI progression.
Main Methods:
- Established a POD model in aged MCI rats using sevoflurane anesthesia and orthopedic surgery.
- Assessed cognitive function using multimodal magnetic resonance imaging (MRI).
- Quantified microglial metabolic activity (glycolysis and OXPHOS) via ECAR and OCR; modulated RUVBL2 expression using lentivirus.
Main Results:
- Postoperative microglia shifted from OXPHOS to glycolysis, with RUVBL2 levels correlating positively with POD.
- Elevated RUVBL2 drove metabolic reprogramming; RUVBL2 knockdown reversed this, reducing neuroinflammation and SG aggregation.
- RUVBL2 knockdown improved cognitive deficits and neural activity, enhancing OXPHOS and reducing glycolysis in microglia.
Conclusions:
- RUVBL2 critically regulates POD by driving microglial metabolic reprogramming.
- Metabolic reprogramming presents a novel therapeutic target for POD.
- RUVBL2 is a potential intervention target for mitigating POD and its progression to cognitive impairment.
