Effects of memantine on mitochondrial function
Jenna McAllister1, Sangeeta Ghosh, Diana Berry
1Department of Neurology, University of Virginia School of Medicine, 800394 McKim Hall, Charlottesville, VA 22908, United States.
Biochemical Pharmacology
|December 7, 2007
Summary
Memantine impacts mitochondrial function, affecting electron transport chain enzymes and peroxide production. These acute and chronic effects differ, with some direct mediation by micromolar concentrations.
Area of Science:
- Neuroscience
- Mitochondrial Biology
- Pharmacology
Background:
- N-methyl-D-aspartate (NMDA) receptor complex is linked to mitochondrial function.
- Memantine, an NMDA receptor antagonist, is used clinically.
- Understanding memantine's direct effects on mitochondria is crucial.
Purpose of the Study:
- To investigate the in vitro effects of acute and chronic memantine exposure on mitochondrial function.
- To determine if NMDA receptor antagonist aminophosphonovaleric acid (APV) modifies memantine's mitochondrial effects.
Main Methods:
- Isolated mitochondria from NT2 cells were exposed acutely to memantine (up to 60uM).
- NT2 cells were chronically exposed to memantine (up to 60uM) for at least two weeks.
- Assays included electron transport chain (ETC) enzyme activity, peroxide production, oxidative stress, calcium, and mitochondrial DNA levels.
Main Results:
- Both acute and chronic memantine affected Complex I (Vmax increased) and Complex IV (Vmax decreased) at high concentrations.
- Acute memantine exposure reduced mitochondrial peroxide production, while chronic exposure increased it.
- APV did not alter the effects of chronic memantine on citrate synthase and Complex IV.
Conclusions:
- Micromolar concentrations of memantine directly affect mitochondrial function.
- Acute and chronic memantine exposures can have distinct impacts on mitochondria.
- Further research is needed to elucidate the precise mechanisms of memantine's mitochondrial interactions.
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