Hippocampus-based mitochondrial respiratory function decline is responsible for perioperative neurocognitive disorders

Background: Perioperative neurocognitive disorders (PND), a postoperative cognitive dysfunction occurs more often in the elderly. The etiology of PND remains largely elusive. This study aims to understand the etiology in a mouse model with tibial fracture (a surgical trauma), by examining the transcriptome-wide response of hippocampus, a brain region that is tightly associated with memory formation. Methods: Mice at age of 7~8 months were randomly divided into two groups, surgery (tibial fracture) group and control (sham) group. At day (d) 1 after the surgical operation, hippocampal tissues were isolated and then subjected to RNA extraction and RNA sequencing (RNA-seq). Findings: Levels of respiratory complex related genes are significantly decreased in the brain of mice subjected to surgery. Consequently, the activities of multiple respiratory complexes and respiratory chain function is decreased in the hippocampus of mice with surgical operation. Interpretation: We here propose a novel mechanism of mitochondrial dysfunction in PND etiology, and also provide a potential therapeutic target for PND. Mice were randomly allocated to two groups, sham and tibial fracture group. Control group of mice were subjected to anesthesia only, and surgery group of mice were subjected to anesthesia followed with tibial fracture operation. At day 1 of post operation, RNA was isolated from the hippocampus and then subjected to RNA-seq analysis.