Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer ’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

AbstractIntermittent 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 (ISC A1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice.In vivo andin 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.
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research