Elevated silver, barium and strontium in antlers, vegetation and soils sourced from CWD cluster areas: Do Ag/Ba/Sr piezoelectric crystals represent the transmissible pathogenic agent in TSEs?
Introduction
Exceptionally high levels of Ag, Sr and Ba were measured in deer antlers, vegetation, soils sourced from chronic wasting disease (CWD) cluster areas in Colorado, Wisconsin, Saskatchewan, whilst levels were 3-fold, 2.5-fold and 3-fold less (for Ag, Sr, Ba, respectively) in CWD-free areas of Alberta/UK. Ag was virtually undetectable in antlers sampled from CWD-free deer herds in the UK.
These observations were recorded as part of an extensive comparative analytical study of the levels of 46 metals in the soils, water and vegetation of CWD cluster and CWD-free regions conducted across North America. This work represented the North American perspective of a three year globally orientated project designed to establish whether any abnormal mineral profile or abnormal magnetic/radioactive/oxidative capacity is a common characteristic of transmissible spongiform encephalopathie (TSE) cluster ecosystems around the world, and, if so, whether that abnormality plays a primary role in the pathogenesis of TSEs.
Since the primary origins of TSEs are unknown, this study was designed to challenge the theory based upon previously amassed data [1], [2], [3] that high levels of specific metals, such as manganese (Mn) or Ag, in combination with low levels of Cu in the environment may bring about a rogue metal replacement at vacant Cu ligands on the cellular prion protein (PrPc) – a Cu binding protein [4] whose misfolded isoforms hallmark the TSE diseased brain [5].
Section snippets
Does a network of Cu–PrP–Cu-proteoglycan conduits conduct a relay of electric signals that regulate the auditory/circadian associated circuitry of the biosystem?
Since PrPc `knock out' mice develop symptoms (sleep disorders, abnormal EEG, etc.) that indicate an underlying disturbance in the regulation of the nocturnal–diurnal rhythm [6], [7] and GABA inhibitory currents at synapses [4], [5], it has been suggested that PrPc performs some metabolic role in mediating the circadian diurnal–nocturnal rhythm and other external stimuli. In this respect, it has been proposed that the paramagnetic Cu [8] component of the PrP molecule [4] performs a role as a
Ag, Ba, Sr or Mn nucleated crystal-PrP-ferritin complexes disrupt these conduits of electrical signalling throughout the CNS. A primary prerequisite for the pathogenesis of TSEs? (see Fig. 1)
In this respect, the pathogenesis of TSE could be initiated by a disruption at any point along these putative PrP-proteoglycan `conduits' of electrical conduction; ultimately resulting in the overall collapse in both the GABA mediated modulation of neuronal response at the synapses [4] and the proteoglycan regulated anti-oxidant/growth factor signalling systems [21], [28].
Environmental analytical observations in TSE cluster zones suggest that a foreign metal replacement binding on the native
Soil sample collection/analysis method
Each soil sample comprised a 300 g sample drawn from a mix of 20 columns of dry soil bored with a stainless steel auger; each column having been bored at equidistant spaces along a W shape spanning an area of ≈10 acres, the area being representative of the region grazed by the CWD affected deer under study. Each column was drawn from the top soil to a depth of 6 in. having taken care to avoid inclusion of root material/surface organic matter and collection of samples near to gateways,
High silver, possible environmental sources and modes of uptake
High levels of Ag and low levels of Cu were recorded in the antler material, soils and deer browse vegetation drawn from CWD affected zones (see Table 1, Table 2, Graph 1, Graph 2). These results represent the first time that Ag has been detected in antlers, whilst adding some support to the proposal [2], [3] that high Ag and low Cu in the environment may bring about an Ag replacement of vacant Cu ligands on the cellular prion protein (PrPc).
Particularly interesting is the fact that Ag was
Conclusion and future research
Irrespective of any role that elevated levels of Ag, Ba and Sr may play in the pathogenesis of TSEs, the novel observation of Ag in antler might suggest that the antler acts as a hitherto unrecognised toxic `sink' for storing excess intakes of Ag, Ba, Sr and other metals in cervidae who are thriving off foodchains that have bioconcentrated these metals. The toxic load is conveniently shed along with the antler on an annual basis. Or, alternatively, Ag and/or Ba could perform some metabolic role
Acknowledgements
The Fats and Protein Research Foundation, USA, Allan and Judith Pincus, the Fred Foundation, JM and MD Purdey for funding of this project. Thanks to Sarah Simpson for collection of TSE-free Vermont samples, and to Judy Cabay, Kay Sinclair, Shirley Parrish, Mark and Linda Kessenich, Gene Flees, Ken Dolores and the Ruell family for assisting with antler/soil collection. Thanks to Dr. David Grant (Aberdeen) and Dr. Thad Mauney (Billings, Montana) for enlightening education over the biochemistry of
References (68)
Ecosystems supporting clusters of sporadic TSEs demonstrate excesses of the radical generating divalent cation, manganese, and deficiencies of antioxidant co factors Cu, Se, Fe, Zn: does a foreign cation substitution at Prp's Cu domain initiate TSE?
Med. Hypotheses
(2000)Does an infrasonic acoustic shock wave resonance of the Mn 3+ loaded/Cu depleted prion protein initiate the pathogenesis of TSE?
Med. Hypotheses
(2003)Prion and prejudice; normal protein and the synapse
Trends Neurosci.
(2001)- et al.
Circadian regulation of PrP messenger RNA in rat forebrain; a widespread and synchronous rhythm
Neuroscience
(1999) Nerve growth factor induces gene expression of PrP and amyloid protein precursor in the developing hamster CNS
Prog. Brain Res.
(1990)- et al.
The key role of the nerve membrane protein PrP in scrapie-like diseases
Sem. Neurosci.
(1991) - et al.
Divalent cations and heparin/heparan sulphate cooperate to control assembly and activity of the fibroblast growth factor receptor complex
The Am. Soc. Biochem. Mol. Biol.
(1996) - et al.
Sulfated glycans stimulate endocytosis of the cellular isoform of the prion protein in cultured cells
The Am. Soc. Biochem. Mol. Biol.
(1995) Pharmacology and toxicology of heavy metals: silver
Pharmac. Ther. A
(1976)- et al.
10E4 antigen of scrapie lesions contains an unusual nonsulfated heparin motif
J. Biol. Chem.
(2001)
The manganese loaded/copper depleted bovine brain fails to neutralise incoming shockbursts of low frequency infrasound; the origins of BSE?
Cattle Practice
Altered circadian activity rhythms and sleep in mice devoid of PrP
Nature
Magnetochemistry
Textbook of biochemistry with clinical correlations
Biological effects of noise
Sensory ecology
Circadian variation and cell division of the mouse alimentary tract, bone marrow and corneal epithelium
Anat. Rec.
Melatonin receptors in the retina, brain and pituitary
Transmissions to mice indicate that new variant CJD is caused by the BSE agent
Nature
Infrared spectroscopy of heparin-cation complexes
Biochem. J.
A potentiometric titration study of the interaction of heparin with metal cations
Biochem. J.
Sulphated glycoaminoglycans prevent neurotoxicity of a human prion protein fragment
Biochem. J.
Observations on kuru 111: pathological features in 5 cases
Aust. Ann. Med.
A retinopathy in sheep affected with Natural Scrapie
Res. Vet. Sci.
A Novel Progressive Spongiform Encephalopathy Vet Record
Spongiform degeneration in mahoganoid mutant mice
Science
Nature
Chemistry; concepts and models
The body electric; electromagnetism and the foundation of life
Nature (London)
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