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

IF 3.2 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2026-02-01 Epub Date: 2025-12-03 DOI:10.1016/j.brainres.2025.150087

Na Zhou , Yan Wang

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Abstract

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.

Abstract Image

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MICU1促进Ca2+稳态和抑制铁下垂，以减轻术后认知功能障碍大鼠的脑组织损伤。

目的：术后认知功能障碍（POCD）在麻醉术后患者中较为严重。本研究探讨MICU1调控POCD大鼠Ca2+稳态和铁下垂的机制。方法：建立POCD大鼠模型，取CA1区海马组织检测MICU1表达。将携带Ad-MICU1或铁下垂诱导剂Erastin的慢病毒注入POCD大鼠右侧脑室，评估其运动功能、学习能力和记忆能力。采用ELISA法检测炎症因子。采用Nissl染色、NeuN染色、HE染色观察神经元形态学变化、海马CA1亚区存活神经元及神经元定位。ELISA法检测CA1区大鼠海马组织中ATP、Ca2+、Fe2+、MDA、SOD、LPO、GSH水平。流式细胞术检测总ROS水平、线粒体ROS水平和线粒体MPP。采用Seahorse XFe 96分析仪测定线粒体耗氧量。Western blot检测凋亡相关蛋白水平。结果：POCD大鼠MICU1降低。MICU1过表达可部分改善POCD大鼠的运动功能、学习能力和记忆能力，减轻中枢炎症和海马神经元损伤。MICU1维持Ca2+稳态，降低Ca2+、总ROS和线粒体ROS水平，并抑制铁下垂。Erastin部分逆转了MICU1过表达对POCD大鼠的有益作用。结论：MICU1促进Ca2+稳态，抑制铁下垂和ROS的产生，减轻POCD大鼠脑组织损伤。

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来源期刊

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.