Transcranial Direct Current Stimulation (tDCS) Induces Adrenergic Receptor-Dependent Microglial Morphological Changes...

Area of Science:

• Neuroscience
• Glial Cell Biology
• Neuroimmunology

Background:

• Transcranial direct current stimulation (tDCS) shows therapeutic potential for cognitive enhancement and neurological disorders.
• Astrocytes exhibit calcium (Ca2+) elevations during tDCS, but tDCS effects on microglia remain largely unexplored.
• Microglia, the brain's resident immune cells, play crucial roles in neural function and disease.

Purpose of the Study:

• To investigate the impact of tDCS on microglial morphology and behavior in a rodent model.
• To determine the cellular and molecular mechanisms underlying tDCS-induced microglial changes.
• To explore the potential interaction between astrocytes and microglia in tDCS effects.

Main Methods:

• Histological analysis of Iba-1 immunohistochemistry to assess microglial morphology.
• In vivo two-photon imaging to track microglial motility.
• Pharmacological blockade of adrenergic receptors and use of IP₃R2-deficient mice.

Main Results:

• tDCS in awake mice caused significant changes in microglial morphology (enlarged somata) and reduced motility.
• These tDCS effects were dependent on astrocyte Ca2+ signaling (IP₃R2-dependent) and noradrenergic pathways (β₂-adrenergic receptor).
• No significant microglial changes were observed in isoflurane-anesthetized mice.

Conclusions:

• tDCS modulates microglial activity in a state-dependent manner (awake vs. anesthetized).
• Astrocyte Ca2+ signaling and noradrenaline are critical mediators of tDCS effects on microglia.
• Findings suggest a complex interplay between astrocytes and microglia in mediating functional outcomes of tDCS.