Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie

Autor: R, Bolea, P, Hortells, I, Martín-Burriel, A, Vargas, B, Ryffel, M, Monzón, J J, Badiola
Přispěvatelé: Research Centre for Prion Diseases, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Immunologie et Embryologie Moléculaires (IEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Zdroj: Neuropathology and Applied Neurobiology
Neuropathology and Applied Neurobiology, Wiley, 2010, 36 (4), pp.300-11. ⟨10.1111/j.1365-2990.2010.01065.x⟩
ISSN: 0305-1846
1365-2990
DOI: 10.1111/j.1365-2990.2010.01065.x⟩
Popis: International audience; 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.
Databáze: OpenAIRE