Related Experiment Videos
Dopamine neurotoxicity in cortical neurons
S Alagarsamy1, M Phillips, T Pappas
1Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Drug and Alcohol Dependence
|November 18, 1997
Summary
Dopamine (DA) at concentrations of 10-100 microM causes cortical neuron death by forming reactive oxygen species. This neurotoxicity is reduced by antioxidants and iron chelators, suggesting a role for oxidative stress in dopamine-induced injury.
Area of Science:
- Neuroscience
- Cell Biology
- Toxicology
Background:
- Dopamine (DA) toxicity is known at high concentrations (>100 microM) in various neuronal cultures.
- DA may contribute to neurotoxicity from N-methyl-D-aspartate receptor antagonists in vivo.
- The specific toxicity of DA in cortical neurons requires further investigation.
Purpose of the Study:
- To determine the in vitro toxicity of dopamine (DA) in primary cortical cell cultures.
- To elucidate the mechanism underlying DA-induced cortical neurotoxicity.
- To assess the role of oxidative stress and DA uptake in this toxicity.
Main Methods:
- Primary cortical cell cultures were treated with varying concentrations of DA (10-100 microM).
- Cell viability was assessed using calcein and ethidium homodimer fluorescence.
- Lactate dehydrogenase (LDH) release was measured to quantify cell damage.
- The effects of antioxidants (superoxide dismutase/catalase), an iron chelator (deferoxamine), and DA uptake inhibitors (nomifensine) were evaluated.
Main Results:
- DA treatment (10-100 microM) for 24 hours caused a concentration-dependent increase in dead cortical cells.
- DA-induced cell death was significantly reduced by superoxide dismutase/catalase and deferoxamine.
- DA increased LDH release, an effect inhibited by antioxidants and deferoxamine, and potentiated by nomifensine.
- D1 and D2 receptor antagonists did not prevent DA-induced LDH release.
Conclusions:
- Low to moderate concentrations of dopamine (DA) are toxic to cortical neurons in vitro.
- DA-induced neurotoxicity likely involves autooxidation and the formation of reactive oxygen species (ROS), such as superoxide and hydroxyl radicals.
- The findings suggest that oxidative stress, not receptor activation, mediates DA toxicity in cortical neurons, potentially relevant to psychomotor stimulant effects but not fully explaining in vivo neurotoxicity of NMDA antagonists.