Astrocyte Ca2+ waves trigger responses in microglial cells in brain slices

Area of Science:

• Neuroscience
• Cell Biology
• Neuroimmunology

Background:

• Pathologic brain events trigger widespread microglial cell activation, extending beyond the injury zone.
• Microglial cells play a crucial role in brain injury responses.

Purpose of the Study:

• To investigate whether glial calcium (Ca2+) waves can activate microglial cells.
• To elucidate the mechanisms underlying glial Ca2+ wave propagation and its effect on different glial cell types.

Main Methods:

• Elicited Ca2+ waves in corpus callosum glial cells using electrical stimulation or adenosine triphosphate (ATP) ejection in acute brain slices.
• Utilized Ca2+-sensitive dyes and enhanced green fluorescence protein (EGFP)-labeled astrocytes to identify reacting cell populations.
• Recorded microglial cell membrane currents using patch-clamp technique after labeling with dye-coupled lectin.

Main Results:

• Glial Ca2+ waves activated Ca2+ responses in both astrocytes and non-astrocytic glial cells, spreading over hundreds of micrometers.
• Regenerative ATP release and metabotropic purinergic receptor activation mediated wave propagation, confirmed by blockade with Reactive Blue 2.
• Microglial cells exhibited purinergic responses when the Ca2+ wave passed by, indicating their activation by the wave.

Conclusions:

• Glial Ca2+ waves are not confined to astrocytes but broadly activate diverse glial cell types, including microglia.
• Adenosine triphosphate (ATP) release and purinergic signaling are key mechanisms driving glial Ca2+ wave propagation and glial cell activation.
• These findings reveal a novel mechanism of intercellular communication in the brain with implications for understanding injury responses.