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.
Highlights
Faraday’s discovery that a changing magnetic field induces a current in a conductor has contributed to many applications, such as the electromagnetic stimulation of body tissues and organs (Barker, Jalinous & Freeston, 1985)
We recently demonstrated that low intensity repetitive magnetic stimulation (LI-rMS) of dissociated cortical neurons rapidly increases levels of intracellular calcium, with higher levels of intracellular calcium detected following 10 Hz compared to 1 Hz stimulation (Grehl et al, 2015)
Spontaneous transmitter release is increased following LI-rMS in excitatory neurons (Ahmed & Wieraszko, 2008), and our results suggest a similar increase in spontaneous GABA release from B50 cells
Summary
Faraday’s discovery that a changing magnetic field induces a current in a conductor has contributed to many applications, such as the electromagnetic stimulation of body tissues and organs (Barker, Jalinous & Freeston, 1985). Electromagnetic stimulation of brain tissue has significant experimental and therapeutic potential because the induction of electric currents within neurons can modulate neuronal excitability, allowing non-invasive investigation and manipulation of brain circuit function and connectivity. It is apparent, that cellular mechanisms underpinning behavioural effects of LI-rTMS remain poorly characterised. In vitro experiments have consistently shown that low intensity repetitive magnetic stimulation (LI-rMS–no cranium) modulates intracellular calcium levels in non-neuronal (Aldinucci et al, 2000; Walleczek & Budinger, 1992; Zhang et al, 2010) and neuronal cells (Grehl et al, 2015)
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