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Akt activation is involved in P2Y12 receptor-mediated chemotaxis of microglia

Yasuhiro Irino1, Yasuko Nakamura, Kazuhide Inoue

  • 1Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan.

Journal of Neuroscience Research
|January 10, 2008
PubMed

Insights

Adenosine diphosphate (ADP) drives microglial cell movement to injured areas through a pathway involving phospholipase C (PLC) and calcium signaling. This process also activates Akt, crucial for microglial chemotaxis in the central nervous system.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Microglia are key immune cells in the central nervous system (CNS) with critical roles in injury response.
  • Microglia exhibit morphological changes and migration towards sites of neural injury.
  • Previous research identified ATP/ADP signaling via the P2Y12 receptor as a driver of microglial chemotaxis.

Purpose of the Study:

  • To elucidate the intracellular signaling mechanisms, specifically phospholipase C (PLC) and calcium pathways, involved in ADP-induced microglial chemotaxis.
  • To investigate the role of Akt activation in P2Y12 receptor-mediated microglial migration.

Main Methods:

  • Utilized pharmacological inhibitors: U73122 (PLC inhibitor) and wortmannin (PI3K inhibitor).
  • Employed a calcium chelator, BAPTA-AM, to assess calcium's role.
  • Measured microglial chemotaxis, intracellular calcium responses, and Akt phosphorylation status.

Main Results:

  • U73122 significantly suppressed microglial chemotaxis and abolished ADP-evoked calcium responses.
  • BAPTA-AM inhibited ADP-induced microglial chemotaxis, confirming the necessity of calcium signaling.
  • ADP stimulation led to Akt phosphorylation, dependent on P2Y12 receptor activation, PLC, calcium, and PI3K.
  • Inhibition of Akt activation resulted in impaired microglial chemotaxis.

Conclusions:

  • ADP-induced microglial chemotaxis is regulated by a phospholipase C-mediated calcium signaling pathway.
  • Akt activation, downstream of PI3K and PLC-mediated calcium increase, is essential for microglial migration towards ADP.
  • These findings reveal key molecular players in the inflammatory response of microglia to neural injury.

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