MICU1 promotes Ca2+ homeostasis and curbs ferroptosis to attenuate brain tissue damage in rats with postoperative cognitive dysfunction

Objective: Postoperative cognitive dysfunction (POCD) is severe in patients after anesthesia and surgery. This study investigates the mechanism by which MICU1 regulates CA²⁺ homeostasis and Ferroptosis in POCD rats.

Methods: A POCD rat model was established, and hippocampal tissue was collected from the CA1 region to assess MICU1 expression. The lentivirus carrying Ad-MICU1 or the Ferroptosis inducer Erastin was injected into the right lateral ventricle of POCD rats, followed by evaluation of motor function, learning ability, and memory capacity. Inflammatory cytokines were measured using ELISA. Nissl staining, NeuN staining, and HE staining were conducted to observe morphological changes in neurons, surviving neurons in the hippocampal CA1 subregion, and neuronal localization. ELISA was performed to assay the levels of ATP, CA²⁺, Fe²⁺, MDA, SOD, LPO, and GSH in rat hippocampal tissue in the CA1 region. Flow cytometry was conducted to measure total ROS levels, mitochondrial ROS levels, and mitochondrial MPP. The Seahorse XFe 96 analyzer was employed to measure the mitochondrial oxygen consumption rate. Western blot was conducted to examine the levels of ferroptosis-related proteins.

Results: MICU1 was reduced in POCD rats. MICU1 overexpression partially improved motor function, learning ability, and memory capacity and alleviated central inflammation and hippocampal neuronal damage in POCD rats. MICU1 maintained CA²⁺ homeostasis, reduced CA²⁺, total ROS, and mitochondrial ROS levels, and inhibited Ferroptosis. Erastin partially reversed the beneficial effects of MICU1 overexpression on POCD rats.

Conclusion: MICU1 promotes CA²⁺ homeostasis, inhibits Ferroptosis and ROS production, and alleviates brain tissue damage in POCD rats.

Brain tissue damage; Ca(2+) homeostasis; Ferroptosis; MICU1; Postoperative cognitive dysfunction.