Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice
Yang Zhu1 · Hao Huang1 · Zhi Chen3 · Yong Tao1 · Ling‑Yi Liao1 · Shi‑Hao Gao1 · Yan‑Jiang Wang2 · Chang‑Yue Gao11 Department of Rehabilitation Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China
2 Department of Neurology and Center for Clinical Neuroscience, Daping Hospital, Army Medical University, Chongqing 400042, China
3 Department of Special Medicine, Daping Hospital, Army Medical University, Chongqing 400042, China
Abstract
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.
Keywords
Intermittent theta burst stimulation; Alzheimer’s disease; Iron-sulfur cluster assembly 1; Mitochondrial dysfunction; Neurodegeneration
