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

Abstract

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.

• Authors: R Bolea, P Hortells, I Martín-Burriel, A Vargas, B Ryffel, M Monzón, J J Badiola
• Journal: Neuropathology and applied neurobiology (Neuropathol Appl Neurobiol) Vol. 36 Issue 4 Pg. 300-11 (Jun 2010) ISSN: 1365-2990 [Electronic] England
• PMID: 20070537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bax protein, mouse
• DNA-Binding Proteins
• Nerve Tissue Proteins
• NeuN protein, mouse
• Nuclear Proteins
• Plfr protein, mouse
• Pregnancy Proteins
• bcl-2-Associated X Protein
• Manganese
• Copper
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Apoptosis (physiology)
• Brain (metabolism)
• Caspase 3
• Copper (administration & dosage, deficiency, metabolism)
• DNA-Binding Proteins
• 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)