In vivo treatment with diphenyl ditelluride induces neurodegeneration in striatum of young rats: Implications of MAPK and Akt pathways
| Autor: | Letícia Ferreira Pettenuzzo, Carlos Alberto Gonçalves, Regina Pessoa-Pureur, Márcio Ferreira Dutra, Luana Heimfarth, Fátima Theresinha Costa Rodrigues Guma, João Rocha, Claudia Marlise Balbinotti Andrade, Samanta Oliveira Loureiro |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cell signaling Neurofilament Blotting Western Population Apoptosis Astrogliosis Biology Real-Time Polymerase Chain Reaction Toxicology Striatum chemistry.chemical_compound Benzene Derivatives Organometallic Compounds medicine Animals Homeostasis Gliosis Rats Wistar education Protein kinase B Cytoskeleton Neurons Pharmacology education.field_of_study Neurodegeneration Diphenyl ditelluride Neurodegenerative Diseases Flow Cytometry medicine.disease Immunohistochemistry Rats Cell biology Neostriatum Oncogene Protein v-akt Cytoskeletal Proteins medicine.anatomical_structure nervous system chemistry biology.protein Electrophoresis Polyacrylamide Gel Female Neurotoxicity Syndromes Mitogen-Activated Protein Kinases NeuN Phosphorus Radioisotopes Astrocyte |
| Zdroj: | Toxicology and Applied Pharmacology. 264(2):143-152 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2012.07.025 |
| Popis: | In the present report 15day-old Wistar rats were injected with 0.3μmol of diphenyl ditelluride (PhTe)(2)/kg body weight and parameters of neurodegeneration were analyzed in slices from striatum 6days afterwards. We found hyperphosphorylation of intermediate filament (IF) proteins from astrocyte (glial fibrillary acidic protein-GFAP and vimentin) and from neuron (low-, medium- and high molecular weight neurofilament subunits: NF-L, NF-M and NF-H, respectively) and increased MAPK (Erk, JNK and p38MAPK) as well as PKA activities. The treatment induced reactive astrogliosis in the striatum, evidenced by increased GFAP and vimentin immunocontent as well as their mRNA overexpression. Also, (PhTe)(2) significantly increased the propidium iodide (PI) positive cells in NeuN positive population without altering PI incorporation into GFAP positive cells, indicating that in vivo exposure to (PhTe)(2) provoked neuronal damage. Immunohistochemistry showed a dramatic increase of GFAP staining characteristic of reactive astrogliosis. Moreover, increased caspase 3 in (PhTe)(2) treated striatal slices suggested apoptotic cell death. (PhTe)(2) exposure decreased Akt immunoreactivity, however phospho-GSK-3-β (Ser9) was unaltered, suggesting that this kinase is not directly implicated in the neurotoxicity of this compound. Therefore, the present results shed light into the mechanisms of (PhTe)(2)-induced neurodegeneration in rat striatum, evidencing a critical role for the MAPK and Akt signaling pathways and disruption of cytoskeletal homeostasis, which could be related with apoptotic neuronal death and astrogliosis. |
| Databáze: | OpenAIRE |
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