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Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis

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Abstract

Stress can affect the brain and lead to depression; however, the molecular pathogenesis is unclear. An association between stress and stress-induced hypersecretion of glucocorticoids occurs during stress. Dexamethasone (a synthetic glucocorticoid steroid) has been reported to induce apoptosis and increase the activity of monoamine oxidase (MAO) (Youdim et al. 1989). MAO is an enzyme for the degradation of aminergic neurotransmitters; dopamine, noradrenaline and serotonin and dietary amines and MAO inhibitors are classical antidepressant drugs. In this study, we have compared the ability of rasagiline (Azilect) and its main metabolite, R-aminoindan with selegiline (Deprenyl) in prevention of dexamethasone-induced brain cell death employing human neuroblastoma SH-SY5Y cells and glioblastoma 1242-MG cells. Dexamethasone reduced cell viability as measured by MTT test, but rasagiline, selegiline, and 1-R-aminoindan could significantly prevent dexamethasone-induced brain cell death. Among three drugs, rasagiline had the highest neuroprotective effect. Furthermore, the inhibitory effects of these drugs on MAO B catalytic activity and on apoptotic DNA damage (TUNEL staining) were examined. Rasagiline exhibited highest inhibition on MAO B enzymatic activity and prevention on DNA damage as compared to selegiline and 1-R-aminoindan. In summary, the greater neuroprotective effect of rasagiline may be associated with the combination of the parent drug and its metabolite 1-R-aminoindan.

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Acknowledgments

This study was supported by Public Health Service Grants P20 RR17701, a NARSAD Young Investigator Award and an Intramural Research Support grant from The University of Mississippi Medical Center. Shawna Tazik and Shakevia Johnson were supported by the Neuroscience Summer Scholars Program (Department of Psychiatry, University of Mississippi Medical Center) We acknowledge Teva Pharmaceutical Co. (Israel) and Hailin Zheng for synthesizing rasagiline and Dr. B. Westermark for providing 1242-MG cells.

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Authors and Affiliations

  1. Division of Neurobiology and Behavioral Research, Department of Psychiatry and Human Behavior (G-109), University of Mississippi Medical Center, 2500N. State Street, Jackson, MS, 39216, USA

    Shawna Tazik, Shakevia Johnson, Deyin Lu, Chandra Johnson, Craig A. Stockmeier & Xiao-Ming Ou

  2. Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA

    Craig A. Stockmeier

  3. Eve Topf Center, Technion-Rappaport Family Faculty of Medicine, Haifa, Israel

    Moussa B. H. Youdim

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  1. Shawna Tazik
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  2. Shakevia Johnson
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  4. Chandra Johnson
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  7. Xiao-Ming Ou
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Correspondence to Xiao-Ming Ou.

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Tazik, S., Johnson, S., Lu, D. et al. Comparative Neuroprotective Effects of Rasagiline and Aminoindan with Selegiline on Dexamethasone-Induced Brain Cell Apoptosis. Neurotox Res 15, 284–290 (2009). https://doi.org/10.1007/s12640-009-9030-4

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  • DOI: https://doi.org/10.1007/s12640-009-9030-4

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