Cellular and molecular changes to cortical neurons following low intensity repetitive magnetic stimulation at different frequencies

Brain Stimul. Jan-Feb 2015;8(1):114-23. doi: 10.1016/j.brs.2014.09.012. Epub 2014 Oct 16.

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.

Keywords: Calcium signaling; Cortical neurons; Pulsed magnetic fields; Repetitive transcranial magnetic stimulation; rTMS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cell Survival / physiology*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology*
  • Electromagnetic Fields*
  • Gene Expression
  • Mice
  • Neurites / physiology
  • Neuronal Plasticity
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Primary Cell Culture
  • Transcranial Magnetic Stimulation

Substances

  • Calcium