| Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie. | |
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MedLine Citation:
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PMID: 20070537 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS: Copper and manganese levels are altered in mice both lacking PrPc and prion-infected brains. The aim of this study was to analyse the effects of manganese and copper imbalance on neuronal apoptosis in a scrapie-infected Tga20 mouse model. METHODS: Immunoreactivities for the apoptotic proteins Bax and active caspase-3 were evaluated in nine regions of the brain of scrapie-infected and control Tga20 mice treated with one of several diets: depleted cooper (-Cu), loaded manganese (+Mn), depleted copper/loaded manganese (-Cu+Mn) and regular diet. Immunohistochemical determination of NeuN was used to detect possible neuronal loss. RESULTS: Intracellular Bax detection was significantly decreased in animals fed with modified diets, particularly in those treated with copper-depleted diets. A decrease in active caspase-3 was primarily observed in animals fed with enhanced manganese diets. Our results show that the -Cu, -Cu+Mn and +Mn diets protected against apoptosis in scrapie-infected mice. However, NeuN immunolabelling quantification revealed that no diet was sufficient to arrest neuronal death. CONCLUSIONS: With regard to apoptosis induction, the response of Tga20 mice to prion infection was similar to that reported for other mice models. Our results demonstrate the neuroprotective effects of -Cu, -Cu+Mn and +Mn diets in a murine model of scrapie. However, neuronal death induced by infection with prions seems to be independent of apoptosis marker signalling. Moreover, copper-modified diets were neuroprotective against the possible toxicity of the prion transgene in Tga20 control and infected mice even though manganese supplementation could not counteract this toxicity. |
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Authors:
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R Bolea; P Hortells; I Martín-Burriel; A Vargas; B Ryffel; M Monzón; J J Badiola |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-07 |
Journal Detail:
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Title: Neuropathology and applied neurobiology Volume: 36 ISSN: 1365-2990 ISO Abbreviation: Neuropathol. Appl. Neurobiol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-25 Completed Date: 2010-10-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7609829 Medline TA: Neuropathol Appl Neurobiol Country: England |
Other Details:
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Languages: eng Pagination: 300-11 Citation Subset: IM |
Affiliation:
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Animal Pathology Department, University of Zaragoza, Zaragoza, Spain. rbolea@unizar.es |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / physiology* Brain / metabolism* Caspase 3 Copper / administration & dosage, deficiency, metabolism* Diet Disease Models, Animal Manganese / administration & dosage, deficiency, metabolism* Mice Mice, Inbred C57BL Mice, Transgenic Nerve Tissue Proteins / metabolism Neurons / metabolism* Nuclear Proteins / metabolism Pregnancy Proteins / genetics, metabolism Scrapie / diet therapy, metabolism* bcl-2-Associated X Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Bax protein, mouse; 0/Nerve Tissue Proteins; 0/NeuN protein, mouse; 0/Nuclear Proteins; 0/Plfr protein, mouse; 0/Pregnancy Proteins; 0/bcl-2-Associated X Protein; 7439-96-5/Manganese; 7440-50-8/Copper; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Caspase 3 |
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