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Direct current stimulation modulates gene expression in isolated astrocytes with implications for glia-mediated

Limary M Cancel1, Dharia Silas1, Marom Bikson1

  • 1Department of Biomedical Engineering, The City College of New York, Steinman Hall, Room 404C, 160 Convent Ave, New York, NY, 10031, USA.

Scientific Reports
|October 26, 2022
PubMed
Summary

Transcranial direct current stimulation (tDCS) directly alters astrocyte gene expression, suggesting a new mechanism for brain plasticity. This glial-mediated plasticity may enhance tDCS effects in brain disease and cognitive applications.

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Area of Science:

  • Neuroscience
  • Cellular Biology
  • Biophysics

Background:

  • Transcranial direct current stimulation (tDCS) applications in brain disease and cognition depend on lasting changes in brain function.
  • The cellular mechanisms underlying tDCS-induced brain plasticity are not fully understood, particularly the role of astrocytes.
  • Previous work predicted tDCS current concentrates at the blood-brain barrier, exposing endothelial cells (ECs) and astrocytes.

Purpose of the Study:

  • To investigate the direct effects of tDCS on gene expression in astrocytes and brain endothelial cells (ECs).
  • To differentiate the effects of tDCS from those of fluid shear stress on these cell types.

Main Methods:

  • Mouse brain ECs and human astrocytes were subjected to direct current stimulation (DCS) at 0.1 or 1 mA for 10 minutes.
  • Gene expression of neuroactive genes was measured using RT-qPCR immediately and 1 hour post-stimulation.
  • Experiments compared pressure-driven flow alone, pressure-driven flow plus DCS, and DCS alone with blocked flow.

Main Results:

  • DCS directly modulated gene expression in astrocytes (FOS, BDNF), independently of and synergistically with pressure-driven flow.
  • In ECs, pressure-driven flow activated gene expression without additional DCS contribution.
  • DCS alone in ECs showed mixed effects, upregulating FGF9 and downregulating NTF3.

Conclusions:

  • tDCS can directly modulate astrocyte gene expression, proposing a novel glial-mediated plasticity mechanism.
  • This glial-mediated plasticity may be an adjunct mechanism contributing to the therapeutic effects of tDCS.
  • The findings highlight distinct cellular responses of astrocytes and ECs to tDCS and associated fluid dynamics.