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
Keywords: Apoptosis, σ-1R, methamphetamine, microglia.
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