Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie.
OBJECTIVE
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.
Bolea
R
R
Animal Pathology Department, University of Zaragoza, Zaragoza, Spain. rbolea@unizar.es
Hortells
P
P
Martín-Burriel
I
I
Vargas
A
A
Ryffel
B
B
Monzón
M
M
Badiola
J J
JJ
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D053148:Caspase 3; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004032:Diet; D004195:Disease Models, Animal; D008345:Manganese / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012608:Scrapie / Q000178:diet therapy / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; C057074:Plfr protein, mouse; D011257:Pregnancy Proteins; D051028:bcl-2-Associated X Protein; D008345:Manganese; D003300:Copper; C505409:Casp3 protein, mouse; D053148:Caspase 3