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.
Subject(s)
Humans , Mice , Animals , Transcranial Magnetic Stimulation , Alzheimer Disease/therapy , Cognitive Dysfunction/therapy , Cognition , Sulfur , Iron , Iron-Sulfur Proteins , Mitochondrial ProteinsABSTRACT
Diffusion tensor imaging (DTI) can be used to characterize the orientation of water diffusion, and track white matter fiber bundles. The decrease of fractional anisotropy after stroke indicates impairment of structural integrity of fibers, even Wallerian degeneration if serious; in another hand, the increase of fractional anisotropy relates to the more recovery of motor function. The affected/unaffected ratios of fractional anisotropy are more suitable for predicting motor function recovery after stroke. The changes of corticospinal tract in diffusion tensor tractography can also predict the motor outcome in stroke patients.
ABSTRACT
Diffusion tensor imaging (DTI) can be used to characterize the orientation of water diffusion, and track white matter fiber bundles. The decrease of fractional anisotropy after stroke indicates impairment of structural integrity of fibers, even Wallerian degeneration if serious; in another hand, the increase of fractional anisotropy relates to the more recovery of motor function. The affected/unaffected ratios of fractional anisotropy are more suitable for predicting motor function recovery after stroke. The changes of corticospinal tract in diffusion tensor tractography can also predict the motor outcome in stroke patients.