Iron chelator deferiprone rescues memory deficits, hippocampal BDNF levels and antioxidant defenses in an experimental model of memory impairment
| Autor: | Nadja Schröder, Victória Campos Dornelles, Gustavo Dalto Barroso Machado, Ricardo Tavares Monteiro, Luiza Wilges Kist, Henrique Gus, Betânia Souza de Freitas, Luisa Azambuja Alcalde, Pedro Castilhos de Freitas Crivelaro, Maurício Reis Bogo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Hippocampus Tropomyosin receptor kinase B Hippocampal formation medicine.disease_cause Iron Chelating Agents General Biochemistry Genetics and Molecular Biology Antioxidants Biomaterials 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neurotrophic factors Internal medicine Medicine Animals Deferiprone Rats Wistar Memory Disorders biology business.industry Brain-Derived Neurotrophic Factor Neurodegeneration Metals and Alloys medicine.disease Rats Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology chemistry Synaptophysin biology.protein Female General Agricultural and Biological Sciences business 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 31(6) |
| ISSN: | 1572-8773 |
| Popis: | Brain-derived neurotrophic factor (BDNF) plays a key role in neural development and physiology, as well as in pathological states. Post-mortem studies demonstrate that BDNF is reduced in the brains of patients affected by neurodegenerative diseases. Iron accumulation has also been associated to the pathogenesis of neurodegenerative diseases. In rats, iron overload induces persistent memory deficits, increases oxidative stress and apoptotic markers, and decreases the expression of the synaptic marker, synaptophysin. Deferiprone (DFP) is an oral iron chelator used for the treatment of systemic iron overload disorders, and has recently been tested for Parkinson’s disease. Here, we investigated the effects of iron overload on BDNF levels and on mRNA expression of genes encoding TrkB, p75NTR, catalase (CAT) and NQO1. We also aimed at investigating the effects of DFP on iron-induced impairments. Rats received iron or vehicle at postnatal days 12–14 and when adults, received chronic DFP or water (vehicle). Recognition memory was tested 19 days after the beginning of chelation therapy. BDNF measurements and expression analyses in the hippocampus were performed 24 h after the last day of DFP treatment. DFP restored memory and increased hippocampal BDNF levels, ameliorating iron-induced effects. Iron overload in the neonatal period reduced, while treatment with DFP was able to rescue, the expression of antioxidant enzymes CAT and NQO1. |
| Databáze: | OpenAIRE |
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