Abstract
Background and aims
(−)-Deprenyl (selegiline) possesses cyto-protective effect in a much lower concentration,
than it is needed to inhibit MAO-B activity. In permanent MCA occlusion stroke model
in rats, the infarct volume and the number of apoptotic neurons in the penumbra region
were decreased by low concentration (−)deprenyl treatment. Augmented Bcl-2 protein
expression was documented as the responsible factor of this effect. The stabilization
of mitochondrial membrane and diminished ROS production are the further possible consequences
of (−)deprenyl treatment. It is not clear however that (−)deprenyl, or its metabolites
are the acting neuroprotective molecules in the hypoxic/ischemic conditions. We report
here the possible cyto-protective effect of deprenyl-N-oxide (DNO), a recently synthesized
(−)deprenyl metabolite.
Methods
DNO in a very low dose (10−5,−8,−12 M) was tested in PC12 cell culture after hypoxia and in gerbils after transient occlusion
of bilateral common carotid artery. In PC12 culture the cell death was visualized
by PI staining. The level of reactive oxygen species was measured by the Cerium method,
and the mitochondrial membrane integrity was labeled by JC1 staining. Apoptotic neurons
were counted on formaldehyde fixed gerbil brain slices after TUNEL and caspase-3 immune-staining
— NIKON/BIORAD confocal microscopy was used for the quantitative analysis.
Results
DNO treatment significantly decreased the frequency of cell death in PC12 cultures
after hypoxia, increased the mitochondrial transmembrane potential (ΔYm) and decreased the ROS production. In the CA2 regions of gerbil hippocampus, we found
significantly less apoptotic neurons than in the untreated controls.
Conclusion
Transient hypoxia or ischemia induced cell damage could be diminished by DNO. This
(−)deprenyl metabolite is an active cell protective molecule.
Abbreviations:
CLSM (Confocal laser scanning microscopy), ROS (Reactive oxygen species)Keywords
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Article info
Publication history
Published online: March 31, 2009
Identification
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© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
