Frequency-specific effects of repetitive magnetic stimulation on primary astrocyte cultures

Article type: Research Article

Authors: Clarke, Darren^{a; b; 1} | Penrose, Marissa A.^{a; 1} | Penstone, Tamasin^{a; 1} | Fuller-Carter, Paula I.^a | Hool, Livia C.^{b; c} | Harvey, Alan R.^{b; d} | Rodger, Jennifer^{a; d} | Bates, Kristyn A.^{a; *}

Affiliations: [a] School of Biological Sciences, The University of Western Australia, Perth, Crawley, WA, Australia | [b] School of Human Sciences, The University of Western Australia, Perth, Crawley, WA, Australia | [c] Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia | [d] Perron Institute for Neurological and Translational Science, Perth, WA, Australia

Correspondence: [*] Corresponding author: Kristyn A. Bates, MBDP 317 School of Biological Sciences, The University of Western Australia. 35 Stirling Hwy, Perth, WA 6009, Australia. Tel.: +61 08 6488 7515; E-mail: kristyn.bates@uwa.edu.au.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that uses magnetic pulses over the cranium to induce electrical currents in underlying cortical tissue. Although rTMS has shown clinical utility for a number of neurological conditions, we have only limited understanding of how rTMS influences cellular function and cell-cell interactions. Objective:In this study, we sought to investigate whether repeated magnetic stimulation (rMS) can influence astrocyte biology in vitro. Method:We tested four different rMS frequencies and measured the calcium response in primary neonatal astrocyte cultures. We also tested the effect of rMS on astrocyte migration and proliferation in vitro. We tested 3 to 4 culture replicates and 17 to 34 cells for each rMS frequency (sham, 1 Hz, cTBS, 10 Hz and biomemetic high frequency stimulation - BHFS). Results:Of all frequencies tested, 1 Hz stimulation resulted in a statistically significant rise in intracellular calcium in the cytoplasmic and nuclear compartments of the cultured astrocytes. This calcium rise did not affect migration or proliferation in the scratch assay, though astrocyte hypertrophy was reduced in response to 1 Hz rMS, 24 hours post scratch injury. Conclusion:Our results provide preliminary evidence that rMS can influence astrocyte physiology, indicating the potential for a novel mechanism by which rTMS can influence brain activity.

Keywords: Astrocytes, repetitive transcranial magnetic stimulation, calcium signalling, injury

DOI: 10.3233/RNN-160708

Journal: Restorative Neurology and Neuroscience, vol. 35, no. 6, pp. 557-569, 2017