The neurodevelopmental disorder Rett syndrome (RTT) affects mostly females. Upon an apparently normal initial development, cognitive impairment, irregular breathing, motor dysfunction, and epilepsy occur. The complex pathogenesis includes, among others, mitochondrial impairment, redox imbalance, and oxidative damage. As these arise already in neonatal Rett mice, they were proposed contributors of disease progression. Several mitochondrial studies in RTT used either full brains or selected brain regions only. Here, we mapped mitochondria-related ROS generation brain wide. Using sophisticated multi-sample spectrofluorimetry, H₂O₂ release by isolated mitochondria was quantified in a coupled reaction of Amplex UltraRed and horseradish peroxidase. All brain regions and the entire lifespan were characterized in male and female mice. In WT mice, mitochondrial H₂O₂ release was usually highest in cortex and lowest in hippocampus. Maximum rates occurred at postnatal day (PD) 10 and they slightly declined with further maturation. Already at PD 10, male and female Rett mice showed exaggerated mitochondrial H₂O₂ releases in first brain regions and persistent brain-wide increases from PD 50 on. Interestingly, female Rett mice were more intensely affected than male Rett mice, with their brainstem, midbrain and hippocampus being most severely struck. In conclusion, we used a reliable multi-sample cuvette-based assay on mitochondrial ROS release to perform brain-wide analyzes along the entire lifespan. Mitochondrial H₂O₂ release in Rett mice is intensified in all brain regions, affects hemizygous males and heterozygous females, and involves all maturational stages. Therefore, intensified mitochondrial H₂O₂ release seriously needs to be considered throughout RTT pathogenesis and may constitute a potential therapeutic target.

神经发育障碍雷特综合征 (RTT) 主要影响女性。在看似正常的初始发育过程中，会出现认知障碍、不规则呼吸、运动功能障碍和癫痫。复杂的发病机制包括线粒体损伤、氧化还原失衡和氧化损伤等。由于这些已经出现在新生 Rett 小鼠中，因此它们被认为是疾病进展的贡献者。RTT 中的几项线粒体研究使用了完整的大脑或仅选择了大脑区域。在这里，我们绘制了全脑线粒体相关 ROS 生成图。使用复杂的多样品荧光光谱法，H ₂ O ₂在 Amplex UltraRed 和辣根过氧化物酶的偶联反应中量化分离线粒体的释放。所有大脑区域和整个寿命都在雄性和雌性小鼠中进行了表征。在 WT 小鼠中，线粒体 H ₂ O ₂释放通常在皮层最高，在海马最低。最高比率发生在产后第 10 天，并且随着进一步成熟而略有下降。在 PD 10 时，雄性和雌性 Rett 小鼠表现出夸大的线粒体 H ₂ O ₂从 PD 50 开始，第一脑区释放并持续全脑增加。有趣的是，雌性 Rett 小鼠比雄性 Rett 小鼠受到的影响更严重，它们的脑干、中脑和海马体受到的打击最为严重。总之，我们使用可靠的基于多样本比色皿的线粒体 ROS 释放测定来执行整个生命周期的全脑分析。Rett 小鼠的线粒体 H ₂ O ₂释放在所有大脑区域都得到加强，影响半合子雄性和杂合子雌性，并涉及所有成熟阶段。因此，强化线粒体 H ₂ O ₂释放需要在整个 RTT 发病机制中认真考虑，并可能构成潜在的治疗靶点。