Molecular mechanisms involving sigma-1 receptor in cell apoptosis of BV-2 microglial cells induced by methamphetamine

Kai Shen, Yuan Zhang, Xuan Lv, Xufeng Chen, Rongbin Zhou, Lan K. Nguyen, Xiaodong Wu, Honghong Yao

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11 Citations (Scopus)

Abstract

It has been well documented that methamphetamine induces microglial activation and death, however, the molecular mechanisms underlying this process remain poorly understood. In the present study, we demonstrated the involvement of sigma-1 receptor (σ-1R) in methamphetamine-mediated microglial apoptosis. Exposure of BV-2 cells to methamphetamine induces cell apoptosis through its cognate receptor σ-1R, followed by activation of the mitogen-activated protein kinases, phosphatidylinositol-3’ kinase/Akt as well as the downstream transcription factor p53 pathways. Blockage of σ-1R significantly inhibited the increased pro-apoptotic proteins such as Bax, Caspase-3 and Caspase-9 induced by methamphetamine. In conclusion, these findings underscore the critical role of σ-1R in microglial apoptosis induced by methamphetamine. Understanding the link between σ-1R and apoptosis will lead to development of therapeutic strategies targeting methamphetamine-mediated microglial death/dysfunction.

Original languageEnglish
Pages (from-to)857-865
Number of pages9
JournalCNS and Neurological Disorders - Drug Targets
Volume15
Issue number7
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Apoptosis
  • Methamphetamine
  • Microglia
  • σ-1R

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