Stephanie Grehl1, Helena M Viola2, Paula I Fuller-Carter3, Kim W Carter4, Sarah A Dunlop3, Livia C Hool2, Rachel M Sherrard5, Jennifer Rodger6. 1. School of Animal Biology, University of Western Australia, Perth, Australia; Sorbonne Universités, UPMC Univ Paris 06 & CNRS, IBPS-B2A UMR 8256 Biological Adaptation and Ageing, Paris, France. 2. School of Anatomy, Physiology and Human Biology, University of Western Australia, Perth, Australia. 3. School of Animal Biology, University of Western Australia, Perth, Australia. 4. Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Perth, Australia. 5. School of Anatomy, Physiology and Human Biology, University of Western Australia, Perth, Australia; Sorbonne Universités, UPMC Univ Paris 06 & CNRS, IBPS-B2A UMR 8256 Biological Adaptation and Ageing, Paris, France. 6. School of Animal Biology, University of Western Australia, Perth, Australia. Electronic address: jennifer.rodger@uwa.edu.au.
Abstract
BACKGROUND: Repetitive transcranial magnetic stimulation is increasingly used as a treatment for neurological dysfunction. Therapeutic effects have been reported for low intensity rTMS (LI-rTMS) although these remain poorly understood. OBJECTIVE: Our study describes for the first time a systematic comparison of the cellular and molecular changes in neurons in vitro induced by low intensity magnetic stimulation at different frequencies. METHODS: We applied 5 different low intensity repetitive magnetic stimulation (LI-rMS) protocols to neuron-enriched primary cortical cultures for 4 days and assessed survival, and morphological and biochemical change. RESULTS: We show pattern-specific effects of LI-rMS: simple frequency pulse trains (10 Hz and 100 Hz) impaired cell survival, while more complex stimulation patterns (theta-burst and a biomimetic frequency) did not. Moreover, only 1 Hz stimulation modified neuronal morphology, inhibiting neurite outgrowth. To understand mechanisms underlying these differential effects, we measured intracellular calcium concentration during LI-rMS and subsequent changes in gene expression. All LI-rMS frequencies increased intracellular calcium, but rather than influx from the extracellular milieu typical of depolarization, all frequencies induced calcium release from neuronal intracellular stores. Furthermore, we observed pattern-specific changes in expression of genes related to apoptosis and neurite outgrowth, consistent with our morphological data on cell survival and neurite branching. CONCLUSIONS: Thus, in addition to the known effects on cortical excitability and synaptic plasticity, our data demonstrate that LI-rMS can change the survival and structural complexity of neurons. These findings provide a cellular and molecular framework for understanding what low intensity magnetic stimulation may contribute to human rTMS outcomes.
BACKGROUND: Repetitive transcranial magnetic stimulation is increasingly used as a treatment for neurological dysfunction. Therapeutic effects have been reported for low intensity rTMS (LI-rTMS) although these remain poorly understood. OBJECTIVE: Our study describes for the first time a systematic comparison of the cellular and molecular changes in neurons in vitro induced by low intensity magnetic stimulation at different frequencies. METHODS: We applied 5 different low intensity repetitive magnetic stimulation (LI-rMS) protocols to neuron-enriched primary cortical cultures for 4 days and assessed survival, and morphological and biochemical change. RESULTS: We show pattern-specific effects of LI-rMS: simple frequency pulse trains (10 Hz and 100 Hz) impaired cell survival, while more complex stimulation patterns (theta-burst and a biomimetic frequency) did not. Moreover, only 1 Hz stimulation modified neuronal morphology, inhibiting neurite outgrowth. To understand mechanisms underlying these differential effects, we measured intracellular calcium concentration during LI-rMS and subsequent changes in gene expression. All LI-rMS frequencies increased intracellular calcium, but rather than influx from the extracellular milieu typical of depolarization, all frequencies induced calcium release from neuronal intracellular stores. Furthermore, we observed pattern-specific changes in expression of genes related to apoptosis and neurite outgrowth, consistent with our morphological data on cell survival and neurite branching. CONCLUSIONS: Thus, in addition to the known effects on cortical excitability and synaptic plasticity, our data demonstrate that LI-rMS can change the survival and structural complexity of neurons. These findings provide a cellular and molecular framework for understanding what low intensity magnetic stimulation may contribute to human rTMS outcomes.
Authors: Bhedita J Seewoo; Lauren A Hennessy; Liz A Jaeschke; Leah A Mackie; Sarah J Etherington; Sarah A Dunlop; Paul E Croarkin; Jennifer Rodger Journal: J Child Adolesc Psychopharmacol Date: 2021-12-31 Impact factor: 3.031
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Authors: Simone Rossi; Andrea Antal; Sven Bestmann; Marom Bikson; Carmen Brewer; Jürgen Brockmöller; Linda L Carpenter; Massimo Cincotta; Robert Chen; Jeff D Daskalakis; Vincenzo Di Lazzaro; Michael D Fox; Mark S George; Donald Gilbert; Vasilios K Kimiskidis; Giacomo Koch; Risto J Ilmoniemi; Jean Pascal Lefaucheur; Letizia Leocani; Sarah H Lisanby; Carlo Miniussi; Frank Padberg; Alvaro Pascual-Leone; Walter Paulus; Angel V Peterchev; Angelo Quartarone; Alexander Rotenberg; John Rothwell; Paolo M Rossini; Emiliano Santarnecchi; Mouhsin M Shafi; Hartwig R Siebner; Yoshikatzu Ugawa; Eric M Wassermann; Abraham Zangen; Ulf Ziemann; Mark Hallett Journal: Clin Neurophysiol Date: 2020-10-24 Impact factor: 4.861