title: Effect of long-term treatment with rasagiline on cognitive deficits and related molecular cascades in aged mice.
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.
authors.affiliation: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Weinreb
authors.affiliation: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Felix
authors.initials: F
authors.lastname: Badinter
authors.affiliation: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Amit
authors.affiliation: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Bar-Am
authors.affiliation: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: youdim@tx.technion.ac.il.
authors.forename: Moussa B H
authors.initials: MB
authors.lastname: Youdim
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007189:Indans / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013550:Swimming / Q000523:psychology
chemical_list: D002395:Catecholamines; D007189:Indans; D018696:Neuroprotective Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C031967:rasagiline; D008995:Monoamine Oxidase
keywords: Aging; Antidepressant-like behavior; Cognition; Neuroprotection; Neurotrophic parameters; Rasagiline