title: Beneficial behavioral, neurochemical and molecular effects of 1-(R)-aminoindan in aged mice.
abstract: Previous neuroprotective studies demonstrated that 1-(R)-aminoindan (AI), which is the major metabolite of the anti-Parkinsonian drug rasagiline, possesses beneficial pharmacological effects in various cell culture and animal models of neurodegeneration. The present study was aimed at investigating the possible neuroprotective effects of AI on cognitive impairments and neurochemical alterations in aged mice. Our findings provide evidence that following chronic systemic treatment with AI (5 mg/kg; daily; 3 months) of aged mice (24 months old), the compound exerted a significant positive impact on neuropsychiatric functions and cognitive behavior deficits, assessed in a variety of tasks (spatial learning and memory retention, working memory, learning abilities and nest building behavior) and produced an antidepressant-like effect. In addition, chronic AI treatment significantly enhanced expression levels of neurotrophins, including brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF), tyrosine kinase- B (Trk-B) receptor and synaptic plasticity markers, such as synapsin-1 and growth-associated protein-43 (GAP-43) in the striatum and hippocampus in aged mice. Our results also indicate that AI treatment up-regulated the expression levels of the pro-survival Bcl-2 mRNA, increased the anti-apoptotic index Bcl-2/Bax and enhanced the activity of the antioxidant enzyme catalase in the brain of aged mice. These effects of AI were also confirmed in aged rats (24 months old). Altogether, the present findings indicate that AI can induce neuroprotective effects on age-related alterations in neurobehavioral functions and exerts neurotrophic up-regulatory and anti-apoptotic properties in aged animals.
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.
authors.forename: Moussa B H
authors.initials: MB
authors.lastname: Youdim
authors.affiliation: Eve Topf Centers of Excellence for Neurodegenerative Diseases Research, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: worly@tx.technion.ac.il.
authors.forename: Orly
authors.initials: O
authors.lastname: Weinreb
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism / Q000523:psychology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism; D007189:Indans / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008810:Mice, Inbred C57BL; D009425:Nesting Behavior / Q000187:drug effects; D018697:Nootropic Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects; D065852:Spatial Memory / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D007189:Indans; D018697:Nootropic Agents; C016992:1-aminoindan
keywords: 1-(R)-aminoindan; 1-(R)-aminoindan (PubChem CID: 123445); Aging; Cognition; Depressive-like behavior; Neuroprotection; Neurotrophic factors