Exposure to low dietary copper or low copper coupled with high dietary manganese for one year does not alter brain prion protein characteristics in the mature cow

It is now widely accepted that abnormal prion proteins are the likely causative agent in bovine spongiform encephalopathy. Cellular prion proteins ([PrP.sup.c]) bind Cu, which appears to be required to maintain functional characteristics of the protein. The replacement of Cu on [PrP.sup.c] with Mn has resulted in loss of function and increased protease resistance. Twelve mature cows were used to determine the effects of Cu deficiency, alone and coupled with high dietary Mn, on brain Cu and Mn concentrations and on [PrP.sup.c] functional characteristics. Copper-adequate cows were randomly assigned to treatments: 1) control (adequate in Cu and Mn), 2) Cu-deficient (-Cu), and 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. After 360 d, Cu-deficient cows (-Cu and -Cu+Mn) tended to have lesser concentrations of Cu (P = 0.09) in the obex region of the brain stem. Brain Mn tended (P = 0.09) to be greater in -Cu+Mn cattle compared with -Cu cattle. Western blots revealed that [PrP.sup.c] relative optical densities, proteinase K degradability, elution profiles, molecular weights, and glycoform distributions were not different among treatments. The concentration of [PrP.sup.c], as determined by ELISA, was similar across treatment groups. Brain tissue (obex) Mn superoxide dismutase activity was greatest (P = 0.04) in cattle receiving -Cu+Mn, whereas immunopurified [PrP.sup.c] had similar superoxide dismutase-like activities among treatments. Immunopurified [PrP.sup.c] had similar Cu concentrations across treatments, whereas Mn was undetectable. We concluded that Cu deficiency, coupled with excessive Mn intake, in the bovine may decrease brain Cu and increase brain Mn. Copper deficiency, alone or coupled with high dietary Mn, did not cause detectable alterations in [PrP.sup.c] functional characteristics. Key words: bovine, copper, manganese, prion