The Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment and the Brain Lipidome in a Cuprizone-Induced Mouse Model of Demyelination.

Cuihong Zhou,Guangtao Hu,Huaning Wang,Zhengwu Peng,Min Cai,Xianli Wang,Qingrong Tan,Yuezhen Yin,Wenjun Wu,Ying Wang

doi:10.3389/fnins.2021.706786

Abstract

The protective effects of repetitive transcranial magnetic stimulation (rTMS) on myelin integrity have been extensively studied, and growing evidence suggests that rTMS is beneficial in improving cognitive functions and promoting myelin repair. However, the association between cognitive improvement due to rTMS and changes in brain lipids remains elusive. In this study, we used the Y-maze and 3-chamber tests, as well as a mass spectrometry-based lipidomic approach in a CPZ-induced demyelination model in mice to assess the protective effects of rTMS on cuprizone (CPZ)-induced cognitive impairment and evaluate changes in lipid composition in the hippocampus, prefrontal cortex, and striatum. We found that CPZ induced cognitive impairment and remarkable changes in brain lipids, specifically in glycerophospholipids. Moreover, the changes in lipids within the prefrontal cortex were more extensive, compared to those observed in the hippocampus and striatum. Notably, rTMS ameliorated CPZ-induced cognitive impairment and partially normalized CPZ-induced lipid changes. Taken together, our data suggest that rTMS may reverse cognitive behavioral changes caused by CPZ-induced demyelination by modulating the brain lipidome, providing new insights into the therapeutic mechanism of rTMS.

Highlights

Repetitive transcranial magnetic stimulation is a noninvasive intervention widely used to treat several psychiatric disorders, such as major depressive disorder (MDD) (Miron et al, 2019), posttraumatic stress disorder (PTSD) (Philip et al, 2019) and schizophrenia (Jiang et al, 2019)
We found that Repetitive transcranial magnetic stimulation (rTMS) improved cognitive behaviors in CPZ-induced mice and caused changes in various lipid species in the hippocampus, prefrontal cortex (PFC), and striatum, indicating that the re-myelination effect of rTMS might be caused by a region-specific regulation of the brain lipidome
To determine the effects of rTMS on CPZ-induced cognitive impairment, we carried out the Y-maze and 3-chamber tests 24 h after the final rTMS

Summary

Introduction

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive intervention widely used to treat several psychiatric disorders, such as major depressive disorder (MDD) (Miron et al, 2019), posttraumatic stress disorder (PTSD) (Philip et al, 2019) and schizophrenia (Jiang et al, 2019). RTMS has been shown to be beneficial in treating demyelinating disorders, such as Alzheimer’s disease and multiple sclerosis (San et al, 2019; Chou et al, 2020); the protective effects of myelin might be involved in the beneficial effects of rTMS. The role of myelination in cognitive function has been well studied (Geraghty et al, 2019; Kato et al, 2020), and decreased myelin has been implicated in cognitive deficits in various neurological disorders, such as schizophrenia, MDD, and Alzheimer’s disease (Bartzokis et al, 2007; Haroutunian et al, 2014; Li et al, 2016). Diseases affecting myelin are associated with alterations in its lipid composition (Schmitt et al, 2015; Maganti et al, 2019)

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Conclusion