Abstract

In comparison to conventional repetitive transcranial magnetic stimulation (rTMS), theta burst stimulation is stronger and more effective as a brain stimulation approach within short periods. Although this deep rTMS technique is being applied in treating neuropsychiatric disorders, few animal studies have attempted to clarify the neurobiological mechanisms underlying its beneficial effects. This animal study examined the effects of deep rTMS on the cuprizone-induced neuropathologic and behavioral anomalies and explored the underlying mechanism. Adolescent male C57BL/6 mice were fed a rodent chow without or with cuprizone (CPZ; 0.2% w/w) for 5 weeks. Another two groups of mice were subjected to deep rTMS or sham rTMS once a day during weeks 2–5 of the CPZ-feeding period. The behaviors of all mice were assessed after the withdrawal of CPZ before neuropathological and immunological analyses. Compared to the CNT group, mice in CPZ and CPZ + Sham groups showed deficits in social recognition and spatial working memory as well as anxiety-like behavior, in addition to myelin breakdown and OL loss in the corpus callosum (CC), caudate putamen, cerebral cortex, and hippocampus of the brain. Deep rTMS effectively reduced behavioral anomalies and blocked myelin breakdown and OL loss in CPZ-fed mice. Besides, it also dampened microglia activation at lesion sites and rectified cytokines levels (IL-1β, IL-6, and IL-10) in CPZ-affected regions. The most significant effect was seen in the cerebral cortex where alleviated neuropathology co-existed with less microglia activation and higher IL-10 level. These data provided experimental evidence for the beneficial effects of deep rTMS in CPZ-fed mice and revealed a neurobiological mechanism of the modality.

Highlights

  • Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique

  • We found that CPZ-exposed mice displayed more climbing behavior and lower prepulse inhibition at weeks 2 and 3 of the CPZ-exposure period along with higher dopamine but lower norepinephrine levels in the PFC

  • This study aimed to examine the effects of deep repetitive transcranial magnetic stimulation (rTMS) on the neuropathologic changes and behavioral anomalies in CPZ-exposed mice and explore the underlying neurobiological mechanism

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Summary

Introduction

Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique. Via electromagnetic induction, transient and localized electrical fields are generated in the brain cortex, which in turn affect functions of local neurons such as depolarization and firing (Hallett, 2000). The theta-burst stimulation (TBS, a newer modality of rTMS) has been developed and applied in humans. TBS delivers relatively greater and more stimulation to the brain in a shorter period (Huang et al, 2005; Chung et al, 2015). This deep rTMS was shown to change cortical excitability that may last longer than with traditional TMS protocols (Ishikawa et al, 2007; Huang et al, 2009). Recent evidence from human studies supports a therapeutic role of TBS in some neuropsychiatric disorders, which implicates certain brain regions important to cognitive functions (Spronk et al, 2011)

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