Department of Rehabilitation Medicine, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Department of Special Medicine, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Neurosci Bull. 2024 Feb;40(2):182-200. doi: 10.1007/s12264-023-01098-7. Epub 2023 Aug 14.
Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.
间歇性 theta 爆发刺激（iTBS）是一种省时、经济有效的重复经颅磁刺激方案，已被证明可改善阿尔茨海默病（AD）患者的认知功能。然而，iTBS 诱导认知增强的确切机制尚不清楚。先前的研究表明，磁刺激调节线粒体功能。在这里，我们表明 iTBS 可上调 APP/PS1 小鼠大脑中铁硫簇组装 1（ISCA1，线粒体呼吸的必需调节因子）的表达。体内和体外研究表明，iTBS 调节线粒体铁硫簇组装以促进线粒体呼吸和功能，这是 ISCA1 所必需的。此外，iTBS 可挽救 APP/PS1 小鼠的认知下降并减轻 AD 型病理。本研究揭示了 iTBS 通过 ISCA1 介导的铁硫簇组装调节线粒体呼吸和功能的新机制，从而减轻 AD 中的认知障碍和病理。我们为 iTBS 提供了治疗 AD 患者的潜在机制靶点。
