title: Repetitive magnetic stimulation of human-derived neuron-like cells activates cAMP-CREB pathway.
abstract: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulatory technique widely used in research, diagnostics, and neuro-psychiatric therapy. Despite its growing popularity, basic molecular mechanisms underlying the clinical effects of rTMS have remained largely under-researched. Here, we present a human-derived neuronal cell culture system responsive to rTMS effects. SH-SY5Y neuroblastoma cells were differentiated by retinoic acid treatment for 10 days, resulting in a neuronal phenotype characterized by upregulation of neuronal marker proteins and generation of an action potential in response to depolarizing current step injection. Repetitive magnetic stimulation of these cells resulted in increased intracellular cAMP levels and increased phosphorylation of transcription factor CREB. Pretreatment with ketamine (1 μM) potentiated, while pretreatment with lithium (2 mM) attenuated this cellular response to repetitive magnetic stimulation. In conclusion, we introduce here a novel in vitro system responding to rTMS at the level of second messenger signaling. The use of human-derived cells with neuron-like properties will prove useful for further studies on the cellular effects of rTMS.
authors.affiliation: Klinik und Hochschulambulanz für Psychiatrie und Psychotherapie, Charité Campus Benjamin Franklin, Eschenallee 3, 14050, Berlin, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Hellmann
authors.forename: Rene
authors.initials: R
authors.lastname: Jüttner
authors.forename: Clarisse
authors.initials: C
authors.lastname: Roth
authors.forename: Malek
authors.initials: M
authors.lastname: Bajbouj
authors.forename: Imke
authors.initials: I
authors.lastname: Kirste
authors.forename: Isabella
authors.initials: I
authors.lastname: Heuser
authors.forename: Karen
authors.initials: K
authors.lastname: Gertz
authors.forename: Matthias
authors.initials: M
authors.lastname: Endres
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D050882:CREB-Binding Protein / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008094:Lithium / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation
chemical_list: D009419:Nerve Tissue Proteins; D008094:Lithium; D000242:Cyclic AMP; D050882:CREB-Binding Protein