Neurobiology of Aging 2015-09-01

Effect of long-term treatment with rasagiline on cognitive deficits and related molecular cascades in aged mice.

Orly Weinreb, Felix Badinter, Tamar Amit, Orit Bar-Am, Moussa B H Youdim

Index: Neurobiol. Aging 36 , 2628-36, (2015)

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Abstract

The present study aimed to investigate the protective effects of prolonged treatment with the selective, irreversible monoamine oxidase-B inhibitor, novel anti-parkinsonian drug, rasagiline (Azilect) in aged animals. Our findings from behavioral experiments demonstrated that long-term treatment of aged mice with rasagiline (0.2 mg/kg) exerted significant beneficial effects on mood-related dysfunction and spatial learning and memory functions. At this dose of rasagiline, chronic drug administration significantly inhibited monoamine oxidase-B activity and caused an increase in striatal dopamine and serotonin levels, while decreasing their metabolism. In addition, rasagiline treatment elevated striatal mRNA expression levels of dopamine receptors D1 and D2. Furthermore, we found that rasagiline upregulated expression levels of the synaptic plasticity markers brain-derived neurotrophic factor, tyrosine kinase-B receptor, and synapsin-1, increased Bcl-2 to Bax antiapoptotic ratio and the activity of the antioxidant enzyme, catalase in brain of aged mice. The present study demonstrated that long-term treatment with rasagiline could affect behavioral deficits in aged mice and upregulate various neuroprotective parameters in the aging brain, indicating that the drug may have therapeutic potential for treatment of age-associated neurodegenerative disorders.Copyright © 2015 Elsevier Inc. All rights reserved.