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Inhibition of monoamine oxidase activity by repetitive transcranial magnetic stimulation: implications for inter-train interval and frequency

  • Michael Kaczmarczyk
  • Francesca Regen
  • Isabella Heuser
  • Malek Bajbouj
  • Julian Hellmann-Regen
Original Paper

Abstract

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.

Keywords

Monoamine oxidoreductases Major depressive disorder Antidepressant treatment Repetitive transcranial magnetic stimulation Catecholamine homeostasis 

Notes

Acknowledgements

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.

References

  1. 1.
    Bajbouj M, Lisanby SH, Lang UE, Danker-Hopfe H, Heuser I, Neu P (2006) Evidence for impaired cortical inhibition in patients with unipolar major depression. Biol Psychiatry 59(5):395–400PubMedCrossRefGoogle Scholar
  2. 2.
    Bajbouj M, Gallinat J, Lang UE, Hellen F, Vesper J, Lisanby SH, Danker-Hopfe H, Neu P (2007) Motor cortex excitability after vagus nerve stimulation in major depression. J Clin Psychopharmacol 27(2):156–159PubMedCrossRefGoogle Scholar
  3. 3.
    Bajbouj M, Lang UE, Niehaus L, Hellen FE, Heuser I, Neu P (2006) Effects of right unilateral electroconvulsive therapy on motor cortical excitability in depressive patients. J Psychiatr Res 40(4):322–327PubMedCrossRefGoogle Scholar
  4. 4.
    Bajbouj M, Gallinat J, Niehaus L, Lang UE, Roricht S, Meyer BU (2004) Abnormalities of inhibitory neuronal mechanisms in the motor cortex of patients with schizophrenia. Pharmacopsychiatry 37(2):74–80PubMedCrossRefGoogle Scholar
  5. 5.
    Weigand A, Richtermeier A, Feeser M, Guo JS, Briesemeister BB, Grimm S, Bajbouj M (2013) State-dependent effects of prefrontal repetitive transcranial magnetic stimulation on emotional working memory. Brain Stimul 6(6):905–912PubMedCrossRefGoogle Scholar
  6. 6.
    Weigand A, Grimm S, Astalosch A, Guo JS, Briesemeister BB, Lisanby SH, Luber B, Bajbouj M (2013) Lateralized effects of prefrontal repetitive transcranial magnetic stimulation on emotional working memory. Exp Brain Res 227(1):43–52PubMedCrossRefGoogle Scholar
  7. 7.
    Chou YH, Hickey PT, Sundman M, Song AW, Chen NK (2015) Effects of repetitive transcranial magnetic stimulation on motor symptoms in parkinson disease: a systematic review and meta-analysis. JAMA Neurol 72:432–440PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Hoppner J, Berger C, Walter U, Padberg F, Buchmann J, Herwig U, Domes G (2010) Influence of repetitive transcranial magnetic stimulation on special symptoms in depressed patients. Restor Neurol Neurosci 28:577–586PubMedGoogle Scholar
  9. 9.
    Keck ME, Welt T, Post A, Muller MB, Toschi N, Wigger A, Landgraf R, Holsboer F, Engelmann M (2001) Neuroendocrine and behavioral effects of repetitive transcranial magnetic stimulation in a psychopathological animal model are suggestive of antidepressant-like effects. Neuropsychopharmacology 24:337–349PubMedCrossRefGoogle Scholar
  10. 10.
    Miniussi C, Bonato C, Bignotti S, Gazzoli A, Gennarelli M, Pasqualetti P, Tura GB, Ventriglia M, Rossini PM (2005) Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency: an efficacious therapy for major drug-resistant depression? Clin Neurophysiol 116:1062–1071PubMedCrossRefGoogle Scholar
  11. 11.
    Platz T, Rothwell JC (2010) Brain stimulation and brain repair—rTMS: from animal experiment to clinical trials—what do we know? Restor Neurol Neurosci 28:387–398PubMedGoogle Scholar
  12. 12.
    Ridding MC, Rothwell JC (2007) Perspectives—opinion—is there a future for therapeutic use of transcranial magnetic stimulation? Nat Rev Neurosci 8:559–567PubMedCrossRefGoogle Scholar
  13. 13.
    Yukimasa T, Yoshimura R, Tamagawa A, Uozumi T, Shinkai K, Ueda N, Tsuji S, Nakamura J (2006) High-frequency repetitive transcranial magnetic stimulation improves refractory depression by influencing catecholamine and brain-derived neurotrophic factors. Pharmacopsychiatry 39:52–59PubMedCrossRefGoogle Scholar
  14. 14.
    Jakob F, Brakemeier EL, Schommer NC, Quante A, Merkl A, Danker-Hopfe H, Anghelescu I, Heuser I, Bajbouj M (2008) Ultrahigh frequency repetitive transcranial magnetic stimulation in unipolar depression. J Clin Psychopharmacol 28(4):474–476PubMedCrossRefGoogle Scholar
  15. 15.
    Brakemeier EL, Wilbertz G, Rodax S, Danker-Hopfe H, Zinka B, Zwanzger P, Grossheinrich N, Várkuti B, Rupprecht R, Bajbouj M, Padberg F (2008) Patterns of response to repetitive transcranial magnetic stimulation (rTMS) in major depression: replication study in drug-free patients. J Affect Disord 108(1–2):59–70PubMedCrossRefGoogle Scholar
  16. 16.
    Bajbouj M, Brakemeier EL, Schubert F, Lang UE, Neu P, Schindowski C, Danker-Hopfe H (2005) Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder. Exp Neurol 196(2):332–338PubMedCrossRefGoogle Scholar
  17. 17.
    Sehatzadeh SH, Tu HA, Palimaka S, Yap B, O’Reilly D, Bowen J (2016) Repetitive transcranial magnetic stimulation for treatment-resistant depression: a systematic review and meta-analysis of randomized controlled trials. Ont Health Technol Assess Ser 16(5):1–66Google Scholar
  18. 18.
    Cheeran B, Koch G, Stagg CJ, Baig F, Teo J (2010) Transcranial magnetic stimulation: from neurophysiology to pharmacology, molecular biology and genomics. Neurosci Rev J Bring Neurobiol Neurol Psychiatry 16:210–221Google Scholar
  19. 19.
    Funke K, Benali A (2010) Cortical cellular actions of transcranial magnetic stimulation. Restor Neurol Neurosci 28:399–417PubMedGoogle Scholar
  20. 20.
    Kuwabara S, Cappelen-Smith C, Lin CS, Mogyoros I, Burke D (2002) Effects of voluntary activity on the excitability of motor axons in the peroneal nerve. Muscle Nerve 25:176–184PubMedCrossRefGoogle Scholar
  21. 21.
    Hellmann J, Juttner R, Roth C, Bajbouj M, Kirste I, Heuser I, Gertz K, Endres M, Kronenberg G (2012) Repetitive magnetic stimulation of human-derived neuron-like cells activates camp-creb pathway. Eur Arch Psychiatry Clin Neurosci 262:87–91PubMedCrossRefGoogle Scholar
  22. 22.
    Ji RR, Schlaepfer TE, Aizenman CD, Epstein CM, Qiu D, Huang JC, Rupp F (1998) Repetitive transcranial magnetic stimulation activates specific regions in rat brain. Proc Natl Acad Sci USA 95:15635–15640PubMedCrossRefGoogle Scholar
  23. 23.
    Muller MB, Toschi N, Kresse AE, Post A, Keck ME (2000) Long-term repetitive transcranial magnetic stimulation increases the expression of brain-derived neurotrophic factor and cholecystokinin mrna, but not neuropeptide tyrosine mrna in specific areas of rat brain. Neuropsychopharmacology 23:205–215PubMedCrossRefGoogle Scholar
  24. 24.
    Shaul U, Ben-Shachar D, Karry R, Klein E (2003) Modulation of frequency and duration of repetitive magnetic stimulation affects catecholamine levels and tyrosine hydroxylase activity in human neuroblastoma cells: implication for the antidepressant effect of rTMS. Int J Neuropsychopharmacol 6:233–241PubMedCrossRefGoogle Scholar
  25. 25.
    Dean RT, Pollak JK (1985) Endogenous free radical generation may influence proteolysis in mitochondria. Biochem Biophys Res Commun 126:1082–1089PubMedCrossRefGoogle Scholar
  26. 26.
    Dean RT, Thomas SM, Garner A (1986) Free-radical-mediated fragmentation of monoamine oxidase in the mitochondrial membrane. Roles for lipid radicals. Biochem J 240:489–494PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Del Carratore R, Morichetti E, Della Croce C, Bronzetti G (1995) Effect of magnetic fields on rodent monooxygenase enzymes. Bioelectromagnetics 16:324–329PubMedCrossRefGoogle Scholar
  28. 28.
    Eichwald C, Walleczek J (1996) Model for magnetic field effects on radical pair recombination in enzyme kinetics. Biophys J 71:623–631PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Ueno S, Iwasaka M (1996) Catalytic activity of catalase under strong magnetic fields of up to 8 T. J Appl Phys 79:4705–4707CrossRefGoogle Scholar
  30. 30.
    Dunlop BW, Nemeroff CB (2007) The role of dopamine in the pathophysiology of depression. Arch Gen Psychiatry 64(3):327–337PubMedCrossRefGoogle Scholar
  31. 31.
    Shih JC (1991) Molecular basis of human MAO A and B. Neuropsychopharmacology 4(1):1–7PubMedGoogle Scholar
  32. 32.
    Hellmann J, Rommelspacher H, Muhlbauer E, Wernicke C (2010) Raf kinase inhibitor protein enhances neuronal differentiation in human sh-sy5y cells. Dev Neurosci 32:33–46PubMedCrossRefGoogle Scholar
  33. 33.
    Regen F, Le Bret N, Hildebrand M, Herzog I, Heuser I, Hellmann-Regen J (2016) Inhibition of brain retinoic acid catabolism: a mechanism for minocycline’s pleiotropic actions? World J Biol Psychiatry 17:634–640PubMedGoogle Scholar
  34. 34.
    Dunkley PR, Jarvie PE, Robinson PJ (2008) A rapid percoll gradient procedure for preparation of synaptosomes. Nat Protoc 3:1718–1728PubMedCrossRefGoogle Scholar
  35. 35.
    Shulman K, Herrmann N, Walker SE (2013) Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs 27(10):789–797PubMedCrossRefGoogle Scholar
  36. 36.
    Klein E, Shaul U, Karry R, Ben-Shachar D (2002) Modulation of frequency and duration of repetitive magnetic stimulation affects catecholamines and tyrosine hydroxylase in human neuroblastoma cells: implication for the antidepressant effect of rTMS. Biol Psychiatry 51:134 sCrossRefGoogle Scholar
  37. 37.
    Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48:1398–1403PubMedCrossRefGoogle Scholar
  38. 38.
    Rice ME, Cragg SJ, Greenfield SA (1997) Characteristics of electrically evoked somatodendritic dopamine release in substantia nigra and ventral tegmental area in vitro. J Neurophysiol 77:853–862PubMedCrossRefGoogle Scholar
  39. 39.
    George MS, Nahas Z, Molloy M, Speer AM, Oliver NC, Li XB, Arana GW, Risch SC, Ballenger JC (2000) A controlled trial of daily left prefrontal cortex tms for treating depression. Biol Psychiatry 48:962–970PubMedCrossRefGoogle Scholar
  40. 40.
    Kimbrell TA, Little JT, Dunn RT, Frye MA, Greenberg BD, Wassermann EM, Repella JD, Danielson AL, Willis MW, Benson BE, Speer AM, Osuch E, George MS, Post RM (1999) Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism. Biol Psychiatry 46:1603–1613PubMedCrossRefGoogle Scholar
  41. 41.
    Klein E, Kreinin I, Chistyakov A, Koren D, Mecz L, Marmur S, Ben-Shachar D, Feinsod M (1999) Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study. Arch Gen Psychiatry 56:315–320PubMedCrossRefGoogle Scholar
  42. 42.
    Sackeim HA (2000) Repetitive transcranial magnetic stimulation: What are the next steps? Biol Psychiatry 48:959–961PubMedCrossRefGoogle Scholar
  43. 43.
    Speer AM, Kimbrell TA, Wassermann EM, Repella JD, Willis MW, Herscovitch P, Post RM (2000) Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol Psychiatry 48:1133–1141PubMedCrossRefGoogle Scholar
  44. 44.
    McClintock SM, Reti IM, Carpenter LL, McDonald WM, Dubin M, Taylor SF, Cook IA, O’Reardon J, Husain MM, Wall C, Krystal AD, Sampson SM, Morales O, Nelson BG, Latoussakis V, George MS, Lisanby SH, National Network of Depression Centers rTMS Task Group; American Psychiatric Association Council on Research Task Force on Novel Biomarkers and Treatments (2018) Consensus recommendations for the clinical application of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression. J Clin Psychiatry 79(1):35–48CrossRefGoogle Scholar
  45. 45.
    Liboff AR, Jenrow KA (2002) Physical mechanisms in neuroelectromagnetic therapies. Neurorehabilitation 17:9–22PubMedGoogle Scholar
  46. 46.
    Lednev VV (1991) Possible mechanism for the influence of weak magnetic fields on biological systems. Bioelectromagnetics 12:71–75PubMedCrossRefGoogle Scholar
  47. 47.
    Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipović SR, Hummel FC, Jääskeläinen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schönfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L (2014) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 125(11):2150–2206PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik für Psychiatrie und PsychotherapieBerlinGermany

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