Iron Chelators and Antioxidants Regenerate Neuritic Tree and Nigrostriatal Fibers of MPP+/MPTP-Lesioned Dopaminergic Neurons
| Autor: | Carolina Méndez-Gálvez, Christian Gonzalez-Billault, Yorka Muñoz, Natalia Mena, Carlos M. Carrasco, Rodrigo Morales, Bruce K. Cassels, Olimpo García-Beltrán, Patricio Pérez-Henríquez, Marco T. Núñez, Pabla Aguirre |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Neurite Tyrosine 3-Monooxygenase Pyridones Primary Cell Culture Synaptophysin lcsh:Medicine Substantia nigra Pharmacology Biology Deferoxamine Iron Chelating Agents Antioxidants Rats Sprague-Dawley chemistry.chemical_compound Mice 2 2'-Dipyridyl Nerve Fibers Dopamine Mesencephalon medicine Neurites Animals Deferiprone lcsh:Science Multidisciplinary Tyrosine hydroxylase MPTP Dopaminergic Neurons Dopaminergic lcsh:R MPTP Poisoning Rats Mice Inbred C57BL Neuroprotective Agents chemistry G Protein-Coupled Inwardly-Rectifying Potassium Channels 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Hydroxyquinolines Female lcsh:Q Lipid Peroxidation medicine.drug Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 12, p e0144848 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Neuronal death in Parkinson’s disease (PD) is often preceded by axodendritic tree retraction and loss of neuronal functionality. The presence of non-functional but live neurons opens therapeutic possibilities to recover functionality before clinical symptoms develop. Considering that iron accumulation and oxidative damage are conditions commonly found in PD, we tested the possible neuritogenic effects of iron chelators and antioxidant agents. We used three commercial chelators: DFO, deferiprone and 2.2’-dypyridyl, and three 8-hydroxyquinoline-based iron chelators: M30, 7MH and 7DH, and we evaluated their effects in vitro using a mesencephalic cell culture treated with the Parkinsonian toxin MPP+ and in vivo using the MPTP mouse model. All chelators tested promoted the emergence of new tyrosine hydroxylase (TH)-positive processes, increased axodendritic tree length and protected cells against lipoperoxidation. Chelator treatment resulted in the generation of processes containing the presynaptic marker synaptophysin. The antioxidants N-acetylcysteine and dymetylthiourea also enhanced axodendritic tree recovery in vitro, an indication that reducing oxidative tone fosters neuritogenesis in MPP+-damaged neurons. Oral administration to mice of the M30 chelator for 14 days after MPTP treatment resulted in increased TH- and GIRK2-positive nigra cells and nigrostriatal fibers. Our results support a role for oral iron chelators as good candidates for the early treatment of PD, at stages of the disease where there is axodendritic tree retraction without neuronal death. |
| Databáze: | OpenAIRE |
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