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 bovine

¹ Department of Animal Science and Interdepartmental Nutrition Program, North Carolina State University, Raleigh, NC

^* To whom correspondence should be addressed. E-mail: Jerry_Spears{at}ncsu.edu.

	Abstract

It is now widely accepted that abnormal prion proteins are the likely causative agent in bovine spongiform encephalopathy (BSE). Cellular prion proteins (PrP^c) bind copper (Cu), which appears to be required to maintain functional characteristics of the protein. The replacement of Cu on PrP^c with manganese (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 PrP^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 molybdenum (Mo) to further induce Cu deficiency. After 360 d, Cu-deficient cows (-Cu and -Cu+Mn) tended to have less concentrations of Cu (P = 0.09) in the obex region of the brainstem. Brain Mn tended (P = 0.09) to be greater in -Cu+Mn cattle vs. -Cu cattle. Western blots revealed that PrP^c relative optical densities, proteinase K degradability, elution profiles, molecular weights, and glycoform distributions were not different among treatments. The concentration of PrP^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, while immunopurified PrP^c had similar superoxide dismutase-like activities among treatments. Immunopurified PrP^c had similar Cu concentrations across treatments while Mn was undetectable. We conclude 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^c functional characteristics.

Key Words: bovine, copper, manganese, prion

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				L. R. Legleiter, J. W. Spears, and H. C. Liu Copper deficiency in the young bovine results in dramatic decreases in brain copper concentration but does not alter brain prion protein biology J Anim Sci, November 1, 2008; 86(11): 3069 - 3078. [Abstract] [Full Text] [PDF]