Improvement of mouse brain mitochondrial
function after deprenyl treatment

Czerniczyniec A, Bustamante J, Lores-Arnaiz S.
Laboratory of Free Radical Biology,
School of Pharmacy and Biochemistry,
University of Buenos Aires,
Junin 956, C1113AAD,
Buenos Aires, Argentina.
Neuroscience. 2007 Jan 19;144(2):685-93.


Deprenyl is a selective monoamine oxidase (MAO) B inhibitor, widely used for treatment of Parkinson's disease. The present study shows that deprenyl treatment was able to improve mitochondrial function. Fourteen month old mice were injected i.p. with deprenyl (20 mg/kg) and killed 1.5 h after the administration. Different brain subcellular fractions were isolated from control and deprenyl-treated animals to evaluate the effect of deprenyl on nitric oxide synthase (NOS) activity. Oxygen consumption, hydrogen peroxide (H(2)O(2)) production, mitochondrial membrane potential and calcium-induced permeability transition (MPT) were studied in intact mitochondria. In addition, the effect of deprenyl on respiratory complexes and MAO activities were evaluated in submitochondrial particles (SMP). Monoamine oxidase activity was found to be decreased by 55% in mitochondria from deprenyl-treated animals and as a consequence, H(2)O(2) production was significantly decreased. Deprenyl inhibited NOS activity in cytosolic fractions and SMP by 40% and 55%, respectively. In similar conditions, SMP from deprenyl-treated animals showed increased cytochrome oxidase activity. A 51% increase in the oxygen uptake in state 3 (active respiration state) was found after deprenyl treatment, but no significant changes were observed in state 4 (resting respiration state). Deprenyl treatment protected against calcium-induced depolarization and was able to inhibit calcium-induced MPT. This work provides evidence that deprenyl treatment exerts an improvement of brain mitochondrial function, through a reduction of free radical production, prevention of calcium-induced MPT and maintaining a mitochondrial transmembrane potential.

Parkinson's disease
Selegiline and the DAT
Selegiline and the brain
Selegiline and nitric oxide
Selegiline and life-expectancy
Selegiline as an immunostimulant
Selegiline for cocaine-dependence
Selegiline and mitochondrial function
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