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Updated: Jun 11, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Glycogen synthase kinase-3 and p38 MAPK are required for opioid-induced microglia apoptosis

Nanchang Xie1, Hui Li, Dailin Wei

  • 1Department of Neurology, Qilu Hospital, Shandong University, Jinan 250012, China.

Neuropharmacology
|July 6, 2010
PubMed

Insights

Morphine triggers microglia cell death via opioid receptors. This process involves the glycogen synthase kinase-3 beta (GSK-3β) and p38 mitogen-activated protein kinase (MAPK) pathways, leading to apoptosis.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Pharmacology

Background:

  • Opioids are potent analgesics with known adverse effects beyond addiction.
  • Previous research indicated opioids inhibit lymphocyte growth and induce apoptosis.
  • The mechanism of opioid-induced microglia apoptosis remained unclear.

Purpose of the Study:

  • To elucidate the mechanism underlying morphine-induced apoptosis in microglial cells.
  • To investigate the role of opioid receptors, Akt, GSK-3β, and p38 MAPK in this process.

Main Methods:

  • Morphine treatment of BV-2 and primary mouse microglial cells.
  • Assessment of apoptosis and caspase-3 activation.
  • Analysis of phosphorylated Akt (p-Akt) and p-GSK-3β levels.
  • Pharmacological inhibition of GSK-3β and p38 MAPK.

Main Results:

  • Morphine induced microglia apoptosis and caspase-3 activation in an opioid-receptor dependent manner.
  • Morphine decreased p-Akt and p-GSK-3β levels.
  • GSK-3β inhibition potentiated morphine-induced apoptosis and increased phospho-p38 MAPK.
  • p38 MAPK inhibition significantly reduced morphine-induced apoptosis and caspase-3 activation.

Conclusions:

  • Morphine induces microglial apoptosis through opioid receptors.
  • The GSK-3β and p38 MAPK pathways are critical mediators of this effect.
  • These findings reveal a novel mechanism of opioid neurotoxicity in microglia.

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