title: Copper deficiency in the young bovine results in dramatic decreases in brain copper concentration but does not alter brain prion protein biology.
abstract: An Mn for Cu substitution on cellular prion proteins (PrP(c)) in the brain that results in biochemical changes to PrP(c) has been implicated in the pathogenesis of transmissible spongiform encephalopathies. Recent research in the mature bovine does not support this theory. The present study tested this hypothesis by using progeny from gestating cows receiving Cu-deficient diets or Cu-deficient diets coupled with high dietary Mn. Copper-adequate cows (n = 39) were assigned randomly to 1 of 3 treatments: 1) control (adequate in Cu and Mn), 2) Cu deficient (-Cu), or 3) Cu deficient plus high dietary Mn (-Cu+Mn). Cows assigned to treatments -Cu and -Cu+Mn received no supplemental Cu and were supplemented with Mo to further induce Cu deficiency. The -Cu+Mn treatment also received 500 mg of supplemental Mn/kg of dietary DM. Calves were weaned at 180 d and maintained on the same treatments as their respective dams for 260 d. Copper-deficient calves (-Cu and -Cu+Mn) had decreased (P = 0.001) brain (obex) Cu and tended to have increased (P = 0.09) obex Mn relative to control calves. Obex Mn:Cu ratios were substantially increased (P < 0.001) in calves receiving -Cu and -Cu+Mn treatments compared with control calves and were greater (P < 0.001) in -Cu+Mn calves than in -Cu calves. Obex prion protein characteristics, including proteinase K degradability, superoxide dismutase (SOD)-like activity, and glycoform distributions, were largely unaffected. Obex tissue antioxidant capacity was not compromised by perturbations in brain metals, but Cu-deficient calves tended to have decreased (P = 0.06) Cu:Zn SOD activity and increased (P = 0.06) Mn SOD activity. Although obex Cu was decreased because of Cu deficiency and Mn increased because of exposure to high dietary Mn, the obex metal imbalance had minimal effects on PrP(c) functional characteristics in the calves.
authors.affiliation: Department of Animal Science and Interdepartmental Nutrition Program, North Carolina State University, Raleigh 27695, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: Legleiter
authors.forename: J W
authors.initials: JW
authors.lastname: Spears
authors.forename: H C
authors.initials: HC
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001933:Brain Stem / Q000201:enzymology / Q000378:metabolism*; D002417:Cattle / Q000378:metabolism / Q000502:physiology*; D003300:Copper / Q000172:deficiency* / Q000378:metabolism*; D004032:Diet / Q000662:veterinary*; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000032:analysis / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011247:Pregnancy; D011328:Prions / Q000378:metabolism / Q000502:physiology*; D011897:Random Allocation; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D011328:Prions; D008345:Manganese; D003300:Copper; D013482:Superoxide Dismutase; D010447:Peptide Hydrolases