Repetitive low intensity magnetic field stimulation in a neuronal cell line: a metabolomics study

Abstract

Low intensity repetitive magnetic stimulation of neural tissue modulates neuronal excitability and has promising therapeutic potential in the treatment of neurological disorders. However, the underpinning cellular and biochemical mechanisms remain poorly understood. This study investigates the behavioural effects of low intensity repetitive magnetic stimulation (LI-rMS) at a cellular and biochemical level. We delivered LI-rMS (10 mT) at 1 Hz and 10 Hz to B50 rat neuroblastoma cells in vitro for 10 minutes and measured levels of selected metabolites immediately after stimulation. LI-rMS at both frequencies depleted selected tricarboxylic acid (TCA) cycle metabolites without affecting the main energy supplies. Furthermore, LI-rMS effects were frequency-specific with 1 Hz stimulation having stronger effects than 10 Hz. The observed depletion of metabolites suggested that higher spontaneous activity may have led to an increase in GABA release. Although the absence of organised neural circuits and other cellular contributors (e.g., excitatory neurons and glia) in the B50 cell line limits the degree to which our results can be extrapolated to the human brain, the changes we describe provide novel insights into how LI-rMS modulates neural tissue.

A little goes a long way: Neurobiological effects of low intensity rTMS and implications for mechanisms of rTMS

“…All intensities: altered plasma metabolite profile, IPA analysis shows altered metabolic pathways. Glutamine processing and glutamate signalling pathway changes across all intensities Hong et al, (2018) n = 4–6 per group Rat, In Vitro B50 neuroblastoma cells B50 neuroblastoma 1 1 Hz, 10 Hz - 10mins 10 mT (2.2–2.4 mT) Metabolite Assay Changes in 18 metabolites detected. 1 Hz: ↓ 7 amino acids, and 5 other metabolites including cholesterol.…”

“…LI-rTMS has been associated with changes to several metabolites. For example, in B50 rat neuroblastoma cells, an inhibitory neuron-like cell type, an in vitro assay assessed changes in 18 metabolites following a single session of LI-rMS and showed frequency-dependent changes ( Hong et al, 2018 ). 1 Hz stimulation had stronger effects than 10 Hz stimulation, with more metabolites significantly affected (12 vs. 9) and greater fold changes following 1 Hz stimulation ( Hong et al, 2018 ).…”

Extremely low frequency electromagnetic field exposure and restraint stress induce changes on the brain lipid profile of Wistar rats

“…In the present study, lipid damage could be by induction of oxidative imbalance due to chronic exposure, suggesting that chronic ELF-EMF exposure could be like a mild-stressor; this finding is supported by the increase levels in plasma corticosterone concentration and brain lipid peroxidation. Changes in lipid composition, could have deep effects on membrane function by affecting membrane-associated enzymes, receptors and ion channels [ 43 ]. In the present study, different effects of RS and ELF-EMF were found in different brain regions, we speculate that these effects may be mediated by specific mechanisms, like phospholipase [ 30 ] activation by ELF-EMF and genomic and non-genomic effects of glucocorticoids, but these observations deserve further research as has been suggested previously in clinical trials [ 44 ].…”

In Vitro Study of Neurochemical Changes Following Low-Intensity Magnetic Stimulation

“…For instance, high-frequency (HF: >5 Hz) stimulation results in facilitation of neuronal activities, whereas low-frequency (LF: <1 Hz) stimulation reduces neuronal activities [35] [36]. In a previous study, Hong et al [32] measured the depletion of metabolites, which may involve an increase in GABA release, and showed that stimulation at 1 Hz is stronger with respect to these effects than 10-Hz stimulation, but did not identify the frequency-dependent effect correlated with neuronal excitability. In addition, the low-intensity fields are too weak to directly trigger action potential and the neurochemical changes may thus not be immediate but rather cause an increase in excitability by reducing action potential threshold and increasing spike firing potential [31].…”

“…There is evidence that LIMS can modulate brain function in humans [12] and in animal models [24]; however, the cellular and molecular mechanisms underlying the therapeutic effects of LIMS remain poorly understood. A few in vitro and ex vivo studies have demonstrated that LIMS alters gene expression [25], intracellular calcium concentrations in non-neuronal cells [26] [27] [28] and neuronal cells [29], neurobiological changes [30], neuronal excitability [31], and cellular metabolic and biochemical profiles [32]. However, it is still unknown whether LIMS provides facilitation or suppression effects depending on the stimulation protocol.…”