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Updated: Aug 14, 2026
Determination of Mitochondrial Membrane Potential and Reactive Oxygen Species in Live Rat Cortical Neurons
Published on: May 23, 2011
Determining the oxidation states of manganese in NT2 cells and cultured astrocytes
Karlene K Gunter1, Michael Aschner, Lisa M Miller
1Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, 575 Elmwood Ave., Rochester, NY 14642, USA. karlene_gunter@urmc.rochester.edu <karlene_gunter@urmc.rochester.edu>
Abstract:
Excessive brain manganese (Mn) can produce a syndrome called "manganism", which correlates with loss of striatal dopamine and cell death in the striatum and globus pallidus. The prevalent hypothesis for the cause of this syndrome has been oxidation of cell components by the strong oxidizing agent, Mn(3+), either formed by oxidation of intracellular Mn(2+) or transported into the cell as Mn(3+). We have recently used X-ray absorption near edge structure spectroscopy (XANES) to determine the oxidation states of manganese complexes in brain and liver mitochondria and in nerve growth factor (NGF)-induced and non-induced PC12 cells. No evidence was found for stabilization or accumulation of Mn(3+) complexes because of oxidation of Mn(2+) by reactive oxygen species in these tissues. Here we extend these studies of manganese oxidation state to cells of brain origin, human neuroteratocarcinoma (NT2) cells and primary cultures of rat astrocytes. Again we find no evidence for stabilization or accumulation of any Mn(3+) complex derived from oxidation of Mn(2+) under a range of conditions.
Insights
Manganese (Mn) toxicity causes neurological damage. This study found no evidence that the toxic form, Mn(3+), accumulates in brain cells, challenging the long-held hypothesis about manganese-induced neurodegeneration.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Excessive manganese (Mn) in the brain can lead to manganism, a neurotoxic syndrome.
- The prevailing hypothesis suggests that the oxidizing agent Mn(3+) causes striatal dopamine loss and cell death.
- Mn(3+) is thought to arise from intracellular oxidation of Mn(2+) or direct transport into cells.
Purpose of the Study:
- To investigate the oxidation states of manganese complexes in brain-derived cells.
- To determine if Mn(3+) accumulates in human neuroteratocarcinoma (NT2) cells and rat astrocytes.
- To test the hypothesis that Mn(2+) oxidation to Mn(3+) contributes to manganese neurotoxicity.
Main Methods:
- Utilized X-ray absorption near edge structure spectroscopy (XANES) to analyze manganese oxidation states.
- Examined manganese oxidation states in NT2 cells and primary rat astrocyte cultures.
- Studied manganese complexes under various experimental conditions.
Main Results:
- No evidence for the stabilization or accumulation of Mn(3+) complexes was found in brain-derived cells.
- These findings align with previous studies in PC12 cells and brain/liver mitochondria.
- The results indicate that Mn(3+) does not accumulate from Mn(2+) oxidation under tested conditions.
Conclusions:
- The study challenges the prevalent hypothesis implicating accumulated Mn(3+) in manganese-induced neurotoxicity.
- Further research is needed to understand the precise mechanisms of manganese neurodegeneration.
- The findings suggest alternative pathways for manganese toxicity in the brain.
