Zinc-induced neuronal death in cortical neurons
D Lobner1, L M Canzoniero, P Manzerra
1Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cellular and Molecular Biology (Noisy-Le-Grand, France)
|June 30, 2000
Summary
Excessive zinc (Zn2+) exposure causes neurotoxicity. Depending on the concentration, Zn2+ induces either apoptosis or necrosis in brain cells, influencing cell death pathways.
Area of Science:
- Neuroscience
- Cell Biology
- Toxicology
Background:
- Extracellular zinc (Zn2+) plays a role in brain function but can be neurotoxic at high concentrations.
- Understanding the mechanisms of Zn2+-induced neurotoxicity is crucial for brain health.
Purpose of the Study:
- To investigate whether Zn2+ exposure induces apoptosis or necrosis in neuronal cells.
- To elucidate the concentration-dependent effects of Zn2+ on neuronal and glial cell death.
Main Methods:
- Murine neuronal and glial cell cultures were exposed to varying concentrations of ZnCl2 (10-50 microM).
- Neuronal death was assessed by examining chromatin condensation, apoptotic body formation, DNA fragmentation, and sensitivity to inhibitors.
- The role of bax gene and caspase inhibitor (benzyloxycarbonyl-Val-Ala-Asp-CH2F, ZVAD) and NMDA receptor antagonist (D-amino-5-phosphonovalerate, D-APV) were evaluated.
Main Results:
- Low Zn2+ concentrations (20 microM) induced apoptosis, characterized by DNA fragmentation and sensitivity to bax deletion and ZVAD.
- High Zn2+ concentrations (50 microM) induced necrosis, marked by plasma membrane disruption and sensitivity to D-APV.
- Glial cell death was observed at higher Zn2+ concentrations (>30 microM).
Conclusions:
- Zn2+ can trigger distinct cell death pathways, apoptosis or necrosis, based on exposure intensity.
- The findings highlight the dual role of Zn2+ in neuronal cell fate determination.
