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Hippocampus-Based Mitochondrial Respiratory Function Decline Is Responsible for Perioperative Neurocognitive
Keqiang He1, Juan Zhang2,3, Wei Zhang1
1Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Frontiers in Aging Neuroscience
|February 28, 2022
Summary
Perioperative neurocognitive disorders (PNDs) involve impaired mitochondrial function. Surgical trauma reduces respiratory complex components, decreasing ATP production and increasing oxidative stress, revealing a novel PND mechanism.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Geriatrics
Background:
- Perioperative neurocognitive disorders (PNDs) are common in elderly patients after surgery.
- The underlying pathological mechanisms and effective treatments for PNDs remain unclear.
Purpose of the Study:
- To investigate the pathological mechanism of PND using a mouse model of surgical trauma.
- To identify molecular changes in the hippocampus following surgery.
Main Methods:
- A tibial fracture mouse model under anesthesia was used, with control sham surgery.
- Transcriptome-wide analysis and molecular assays were performed on hippocampal tissue at 1 and 3 days post-surgery.
- In vitro experiments using HT22 cells treated with IL-1β were conducted.
Main Results:
- Surgery led to reduced transcript and protein levels of respiratory complex components in the hippocampus.
- Mitochondrial function was impaired, evidenced by decreased ATP production, mitochondrial membrane potential (MMP), and increased reactive oxygen species (ROS).
- Increased IL-1β levels correlated with changes in respiratory complex components, mediated by PGC-1α and NRF-1 transcription factors.
Conclusions:
- Impaired mitochondrial respiratory chain function due to reduced complex components is a novel mechanism underlying PND pathology.
- Cytokine IL-1β plays a key role in mediating these mitochondrial deficits.
- Targeting mitochondrial dysfunction presents a potential therapeutic strategy for PND.

