title: Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease.
abstract: Chronic wasting disease (CWD), the only known wildlife prion disease, affects deer, elk and moose. The disease is an ongoing and expanding problem in both wild and captive North American cervid populations and is difficult to control in part due to the extreme environmental persistence of prions, which can transmit disease years after initial contamination. The role of exogenous factors in CWD transmission and progression is largely unexplored. In an effort to understand the influence of environmental and dietary constituents on CWD, we collected and analyzed water and soil samples from CWD-negative and positive captive cervid facilities, as well as from wild CWD-endozootic areas. Our analysis revealed that, when compared with CWD-positive sites, CWD-negative sites had a significantly higher concentration of magnesium, and a higher magnesium/copper (Mg/Cu) ratio in the water than that from CWD-positive sites. When cevidized transgenic mice were fed a custom diet devoid of Mg and Cu and drinking water with varied Mg/Cu ratios, we found that higher Mg/Cu ratio resulted in significantly longer survival times after intracerebral CWD inoculation. We also detected reduced levels of inflammatory cytokine gene expression in mice fed a modified diet with a higher Mg/Cu ratio compared to those on a standard rodent diet. These findings indicate a role for dietary Mg and Cu in CWD pathogenesis through modulating inflammation in the brain.
authors.affiliation: a National Wildlife Research Center, US Department of Agriculture , Animal and Plant Health Inspection Service, Wildlife Services , Fort Collins , CO , USA;
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Nichols
authors.affiliation: b Colorado State University Diagnostic Laboratory, College of Veterinary Medicine, Colorado State University , Fort Collins , CO , USA;|c Department of Microbiology , Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University Prion Research Center , Fort Collins , CO , USA;
authors.forename: Terry R
authors.initials: TR
authors.lastname: Spraker
authors.affiliation: a National Wildlife Research Center, US Department of Agriculture , Animal and Plant Health Inspection Service, Wildlife Services , Fort Collins , CO , USA;
authors.forename: Thomas
authors.initials: T
authors.lastname: Gidlewski
authors.affiliation: b Colorado State University Diagnostic Laboratory, College of Veterinary Medicine, Colorado State University , Fort Collins , CO , USA;
authors.forename: Bruce
authors.initials: B
authors.lastname: Cummings
authors.affiliation: c Department of Microbiology , Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University Prion Research Center , Fort Collins , CO , USA;
authors.forename: Dana
authors.initials: D
authors.lastname: Hill
authors.affiliation: d Departments of Pathology and Neurology & National Center for Regenerative Medicine , Case Western Reserve University , Cleveland , OH , USA;
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.affiliation: e National and OIE Reference Laboratory for Scrapie and CWD, Canadian Food Inspection Agency , Ottawa , Ontario , Canada.
authors.forename: Aru
authors.initials: A
authors.lastname: Balachandran
authors.affiliation: a National Wildlife Research Center, US Department of Agriculture , Animal and Plant Health Inspection Service, Wildlife Services , Fort Collins , CO , USA;
authors.forename: Kurt C
authors.initials: KC
authors.lastname: VerCauteren
authors.affiliation: c Department of Microbiology , Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University Prion Research Center , Fort Collins , CO , USA;
authors.forename: Mark D
authors.initials: MD
authors.lastname: Zabel
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D001921:Brain / Q000276:immunology / Q000473:pathology; D003300:Copper / Q000032:analysis / Q000276:immunology*; D003670:Deer; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008274:Magnesium / Q000032:analysis / Q000276:immunology*; D008822:Mice, Transgenic; D012987:Soil / Q000737:chemistry; D034081:Wasting Disease, Chronic / Q000150:complications / Q000453:epidemiology / Q000276:immunology* / Q000473:pathology; D014867:Water / Q000737:chemistry
chemical_list: D012987:Soil; D014867:Water; D003300:Copper; D008274:Magnesium
keywords: Cations; chronic wasting disease; copper; environment; iron; magnesium; manganese; metals; prion disease