Repetitive magnetic stimulation of human-derived neuron-like cells activates cAMP-CREB pathway

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 mu M) 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.