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.

Abstract

Transcranial magnetic stimulation (TMS), which is produced by strong non-static magnetic fields, is a non-invasive means to stimulate the cerebral cortex. Studies from recent years show that TMS affects mood in healthy subjects and improves depressive symptoms in patients with major depression. However, the relationship between the clinical efficacy of TMS and stimulation parameters is still obscure. In the present study we have investigated the effects of different stimulation frequencies and number of treatments on catecholamine turnover in SH-SY5Y cell cultures. A single session of magnetic stimulation (1.7 T) caused a significant decrease in intracellular dopamine and L-DOPA and in noradrenaline (NE) release at a rate of 3 Hz for 10 s but increased NE release at a rate of 9 Hz. These alterations were associated with a reduction (47.8%) or an increase (48%) in tyrosine hydroxylase (TH) activity after 3 and 9 Hz magnetic stimulation, respectively. The latter may be related to the known sensitivity of TH to neuronal firing rates and NE concentrations. Higher stimulation frequencies (15, 20, 45 Hz) had no effect on catecholamine metabolism. Unlike 3 Hz acute treatment, chronic treatment (3 Hz, 11 sessions, for 4 d) had no effect on monoamines and TH activity was increased by 54.5% with no change in its protein level. The results of the present study demonstrate that in tissue culture system frequency and treatment duration of the magnetic stimulation are important factors in affecting catecholamine turnover. Considering the major role of catecholamine in the pathophysiology of depression, these findings may be of relevance to the application of rTMS in humans with major depression.