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

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.