Inhibition of Monoamine Oxidase-A Increases Respiration in Isolated Mouse Cortical Mitochondria

Exp Neurol, 2023 · DOI: 10.1016/j.expneurol.2023.114356 · Published: May 1, 2023

Simple Explanation

Monoamine oxidase (MAO) is an enzyme on the outer mitochondrial membrane that metabolizes amine substrates like serotonin, norepinephrine, and dopamine. Inhibiting MAO-A with clorgyline can increase mitochondrial oxygen consumption, suggesting a boost in energy production within brain cells. The study found that lower doses of clorgyline increased respiration in isolated mitochondria, while a high dose inhibited respiration and increased ROS production. This suggests a potential beneficial range for MAO-A inhibitors regarding mitochondrial health. The research indicates that MAO-A inhibition, but not MAO-B inhibition, affects mitochondrial function. Given that MAO-A is more prevalent in neurons, this suggests a neuron-specific impact of MAO-A inhibitors, potentially relevant for treating neurodegenerative diseases.

Study Duration

Not specified

Participants

22 8-10-week-old male C57BL/6 mice

Evidence Level

Not specified

Key Findings

1
Selective inhibition of MAO-A by clorgyline increased mitochondrial oxygen consumption rate in State V(CI) respiration compared to vehicle treatment.
2
Low doses (5-20μM) of clorgyline increased oxygen consumption rates across the majority of respiration states, while 80μM clorgyline inhibited bioenergetics.
3
80μM clorgyline reduced Complex I and Complex II activities, but no significant changes in Complex IV activity.

Research Summary

This study investigates the direct effects of MAO inhibitors on brain mitochondrial bioenergetics and ROS production. The research focuses on clorgyline (MAO-A inhibitor), deprenyl/rasagiline (MAO-B inhibitors), and pargyline (MAO-A/B inhibitor) using mitochondria isolated from mouse cortex. The findings show that clorgyline, specifically, impacts mitochondrial respiration in a dose-dependent manner. Lower doses enhance respiration, while a higher dose inhibits it and increases ROS production, indicating a potential therapeutic window. The study suggests that MAO-A inhibition may have a beneficial effect on brain mitochondrial health at lower doses, which could be relevant for treating neurodegenerative diseases, stroke, or brain trauma. The researchers also highlight the higher ratio of MAO-A to MAO-B in synaptic mitochondria.

Practical Implications

Therapeutic Potential

MAO-A inhibitors may offer a therapeutic avenue for improving mitochondrial function in neurodegenerative diseases, stroke, and traumatic brain injury.

Dosage Considerations

Careful consideration of dosage is crucial, as high doses of clorgyline can be detrimental to mitochondrial function.

Targeted Treatment

MAO-A inhibitors could be particularly effective in targeting neuronal mitochondrial dysfunction due to the higher concentration of MAO-A in neuronal mitochondria.

Study Limitations

1
The lack of MAO substrates present during these experiments.
2
The effects of acute MAO inhibition on mitochondria function, compared to chronic inhibition achieved by daily dosing in humans.
3
The study did not look at specific cell types.

Your Feedback

Was this summary helpful?

Back to Pharmacology