Chronic intranasal deferoxamine ameliorates motor defects and pathology in the α-synuclein rAAV Parkinson's model
| Autor: | Noemie Tentillier, Fabia Febbraro, Marina Romero-Ramos, Kathrine J. Andersen, Vanesa Sanchez-Guajardo |
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| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Dextroamphetamine Time Factors Tyrosine 3-Monooxygenase Central nervous system Genetic Vectors Antigens Differentiation Myelomonocytic Siderophores Substantia nigra Nerve Tissue Proteins Deferoxamine Motor Activity Transfection Neuroprotection Rats Sprague-Dawley Developmental Neuroscience Antigens CD Dopaminergic Cell Forelimb medicine Animals Humans Administration Intranasal Cell Line Transformed Microglia business.industry Dopaminergic Neurotoxicity Parkinson Disease medicine.disease Corpus Striatum Recombinant Proteins nervous system diseases Rats Disease Models Animal medicine.anatomical_structure nervous system Neurology Gene Expression Regulation alpha-Synuclein Female business Psychomotor Performance medicine.drug |
| Zdroj: | Febbraro, F, Andersen, K J, Sanchez-Guajardo, V M, Tentillier, N & Romero-Ramos, M 2013, ' Chronic Intranasal Deferoxamine Ameliorates Motor Defects and Pathology in the α-Synuclein rAAV Parkinson's Model ', Experimental Neurology . https://doi.org/10.1016/j.expneurol.2013.03.017 |
| ISSN: | 1090-2430 |
| DOI: | 10.1016/j.expneurol.2013.03.017 |
| Popis: | Parkinson's disease is characterized by neuronal death in the substantia nigra and the presence of intracellular inclusions of α-synuclein in the Lewy bodies. Several lines of data support a role for iron in Parkinson's disease: iron is present in Lewy bodies, iron accumulates in the dopaminergic neurons in the substantia nigra, and Parkinson's disease is correlated with polymorphisms of several genes implicated in iron metabolism. Furthermore, iron can compromise the solubility of α-synuclein through direct interaction and can induce neurotoxicity in vitro. Here, we investigate the possible neuroprotective effect of the iron chelator deferoxamine in vivo to elucidate whether iron chelation can provide meaningful therapy for Parkinson's disease. Hence, we used a Parkinson's disease animal model based on unilateral injection of a recombinant adeno-associated viral vector encoding α-synuclein in the rat midbrain. Rats were treated with a novel deferoxamine delivery approach: 6 mg of the compound was administered intranasally three times a week for 3 or 7 weeks. The behavior of the animals and histopathological changes in the brain were analyzed. Our data show that although intranasal administration of deferoxamine in rats did not protect them from dopaminergic cell death, it did decrease the number of the pathological α-synuclein formations at the terminal level. In addition, this treatment resulted in changes in the immune response and an overall partial improvement in motor behavior. Taken together, our data show that in vivo iron chelation can modulate α-synuclein-induced pathology in the central nervous system. Our data suggest that chronic administration of intranasal deferoxamine may be a valid approach to limiting the mishandling of α-synuclein in the central nervous system observed in Parkinson's disease and slowing disease progression. |
| Databáze: | OpenAIRE |
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