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Ru360 Alleviates Postoperative Cognitive Dysfunction in Aged Mice by Inhibiting MCU-Mediated Mitochondrial
Xiaoxiao Xu1, Bin Zhou1, Jun Liu1
1The First Hospital of Ningbo University, Ningbo, 315211, People's Republic of China.
Neuropsychiatric Disease and Treatment
|July 10, 2023
Summary
Mitochondrial calcium uptake is linked to postoperative cognitive dysfunction (POCD). Inhibiting this process with Ru360 improved cognitive function and reduced neuroinflammation in mice, suggesting a new treatment approach for POCD.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Pharmacology
Background:
- Postoperative cognitive dysfunction (POCD) is a common complication, particularly in aged individuals.
- Mitochondrial calcium homeostasis is critical for neuronal function.
- The role of mitochondrial calcium uniporter (MCU)-mediated function in POCD and its link to neuroinflammation remain unclear.
Purpose of the Study:
- To investigate the association between MCU-mediated mitochondrial function and POCD.
- To elucidate the relationship between mitochondrial dysfunction, neuroinflammation, and POCD.
- To evaluate the therapeutic potential of Ru360, a selective mitochondrial calcium uptake inhibitor, in ameliorating POCD.
Main Methods:
- Aged mice underwent experimental abdominal surgery under anesthesia.
- Behavioral tests (Open field, Novel object recognition, Y Maze) assessed cognitive function.
- Hippocampal tissue analysis included reactive oxygen species (ROS), inflammatory cytokines (IL-1β, IL-6, TNF-α), intra-mitochondrial calcium, mitochondrial membrane potential (MMP), and superoxide dismutase (SOD) activity.
- Protein expression was analyzed using Western blot.
Main Results:
- Ru360 treatment inhibited MCU-mediated mitochondrial dysfunction.
- Neuroinflammation markers were significantly reduced in the hippocampus.
- Mice treated with Ru360 showed improved learning and memory abilities post-surgery.
- Mitochondrial calcium homeostasis was maintained by Ru360.
Conclusions:
- Mitochondrial function is a critical factor in the pathogenesis of POCD.
- Targeting mitochondrial calcium uptake with Ru360 demonstrates therapeutic potential for POCD.
- Improving mitochondrial function represents a promising therapeutic strategy for preventing and treating POCD.

