Inhibition of monoamine oxidase activity by repetitive transcranial magnetic stimulation: implications for inter-train interval and frequency
Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulation technique that stimulates cortical regions via time-varying electromagnetic fields; in several countries this technique has been approved as a treatment for major depressive disorder. One empirically established target in antidepressant pharmacotherapy is the flavin-containing monoamine oxidoreductase (MAO). The function of MAO enzymes is based on oxidation processes that may be sensitive towards strong electromagnetic fields. Therefore, we hypothesized that rTMS-induced electromagnetic fields impact the activity of this enzyme. Using crude synaptosomal cell preparations from human SH-SY5Y neuroblastoma cells and rat cortex as well as viable cells, we assessed the effects of rTMS on MAO-A and -B activity in a well-controlled in vitro set up. In short, samples were stimulated at maximal intensity with an equal number of total stimuli at frequencies of 5, 20, and 100 Hz. Sham stimulation was performed in parallel. Treatment at frequencies of 5 and 20 Hz significantly decreased mainly MAO-B activity in all tissue preparations and species, whereas 100 Hz stimulation remained without effect on any MAO activity. Our results support the hypothesis, that rTMS-induced electromagnetic fields affect MAO activity and provide further evidence for intracellular effects possibly contributing to therapeutic effects of this neuromodulatory method. On a cautionary note, however, our findings are solely based on in vitro evidence.
KeywordsMonoamine oxidoreductases Major depressive disorder Antidepressant treatment Repetitive transcranial magnetic stimulation Catecholamine homeostasis
This work was supported by the Charité Clinician Scientist Program (to Julian Hellmann-Regen), and the Charité Junior Clinician Scientist Program (to Michael Kaczmarczyk), funded by the Charité Universitätsmedizin Berlin and the Berlin Institute of Health. The authors wish to thank Meike Terborg, Rita Benz, and Regina Hill for providing excellent technical assistance.
Compliance with ethical standards
Conflict of interest
All authors declare no conflicts of interest with respect to authorship, research and/or publication of this article.
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