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Molecular Mechanisms Involving Sigma-1 Receptor in Cell Apoptosis of BV-2 Microglial Cells Induced by Methamphetamine
1Department of Pharmacology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China. yaohh@seu.edu.cn.
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.
Insights
Methamphetamine causes microglial cell death via the sigma-1 receptor (σ-1R). Blocking σ-1R protects against this methamphetamine-induced apoptosis, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Methamphetamine (MA) is known to cause microglial activation and death.
- The precise molecular mechanisms driving MA-induced microglial apoptosis are not fully understood.
Purpose of the Study:
- To investigate the role of the sigma-1 receptor (σ-1R) in methamphetamine-induced microglial apoptosis.
- To elucidate the signaling pathways involved in this process.
Main Methods:
- BV-2 microglial cells were exposed to methamphetamine.
- The involvement of σ-1R was assessed by blocking its activity.
- Apoptosis-related proteins (Bax, Caspase-3, Caspase-9) and signaling pathways (MAPK, PI3K/Akt, p53) were analyzed.
Main Results:
- Methamphetamine exposure induced apoptosis in BV-2 cells.
- This apoptosis was mediated through the σ-1R.
- Methamphetamine activated MAPK, PI3K/Akt, and p53 pathways.
- Blocking σ-1R significantly reduced pro-apoptotic proteins like Bax, Caspase-3, and Caspase-9.
Conclusions:
- The sigma-1 receptor (σ-1R) plays a critical role in methamphetamine-induced microglial apoptosis.
- Targeting the σ-1R pathway may offer a therapeutic strategy for mitigating methamphetamine-related neurotoxicity.
