Degeneration of the Cerebellar and Hypothalamo Neurohypophysial Systems in Sheep With Scrapie; And Its Relationship to Human System Degenerations

Beck, Elizabeth; Daniel, P. M.; Parry, H. B.

doi:10.1093/brain/87.1.153

Cited by 107 publications

(28 citation statements)

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“…These fluctuations did not exist for cortisol plasma or urine metabolites due to the dampening effect of the metabolic process on the short-term variations of cortisol secretion (Schelcher et al 1999). When the plasma cortisol metabolites (20 -dihydrocortisol, cortisone) are taken into account, the results of the present experiment are consistent with the observed stimulation of the adrenal function in scrapie-affected ewes demonstrated in a previous study (Schelcher et al 1999) and the enlargement of the adrenal cortex observed in scrapieaffected ewes (Beck et al 1964), in experimentally infected mice (Kim et al 1988) and in hamsters infected with the 139H scrapie strain (Carp et al 1990).…”

Section: Discussionsupporting

confidence: 93%

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Picard‐Hagen

Gayrard²,

Alvinerie³

et al. 2000

Journal of Endocrinology

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Naturally scrapie-affected ewes present a syndrome of hypercortisolism as evaluated by measuring total plasma cortisol concentrations. The objective of this study was to investigate the plasma protein binding of cortisol and to evaluate the concentration of the biologically active free fraction of cortisol in scrapie-affected ewes. Corticosteroid binding globulin (CBG) binding parameters were evaluated by equilibrium dialysis in 13 naturally scrapie-affected ewes and nine healthy ewes, during two periods of the clinical evolution of the disease. The hypercortisolism of the scrapie-affected ewes was confirmed by a significant increase of the plasma 20 -dihydrocortisol and cortisone concentrations, while total cortisol concentrations, obtained from an isolated sample, did not differ between scrapie-affected and control ewes. The scrapie diagnosis was confirmed by histopathology. The CBG maximal capacity (B max ) was two times lower in scrapieaffected ewes than in healthy ewes (37 32 nM and 73 28 nM respectively). The dissociation constant K d (8·8 3·7 nM and 9·8 3·0 nM respectively) and the non-specific constant value of binding to albumin (1·13 0·18 and 1·14 0·23 respectively) did not differ significantly between diseased and control ewes. The significant increased concentrations of CBG-free cortisol (i.e. both albumin-bound and free cortisol fractions) in scrapie-affected ewes indicates that total plasma cortisol concentration is not an appropriate index of pituitary-adrenocortical hyperactivity.In conclusion, ewes with naturally occurring scrapie display a syndrome of hypercortisolism associated with a lower CBG binding capacity which leads to an overexposure of glucocorticoid-sensitive targets to CBG-free cortisol. The physiopathological consequences of this overexposure on the development of the neurodegenerative process in prion disease are discussed.

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Section: Discussionsupporting

confidence: 93%

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Picard‐Hagen

Gayrard²,

Alvinerie³

et al. 2000

Journal of Endocrinology

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“…2,14,[76][77][78][79][80]110,114,115 At least 10 amino acid polymorphisms in the protein encoding region of the sheep PrP gene have been reported, 23 and alleles at codons 136 and 171 strongly influence susceptibility and resistance. Now determination of PrP genotype and selection for resistant genotypes form an important aspect of programs to control this disease in North America (http://www.aphis.…”

Section: Geneticsmentioning

confidence: 99%

Chronic Wasting Disease

2005

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Abstract. Chronic wasting disease (CWD) is a unique transmissible spongiform encephalopathy (TSE) of mule deer (Odocoileus hemionus), white-tailed deer (O. virginianus), and Rocky Mountain elk (Cervus elaphus nelsoni). The natural history of CWD is incompletely understood, but it differs from scrapie and bovine spongiform encephalopathy (BSE) by virtue of its occurrence in nondomestic and free-ranging species. CWD has many features in common with scrapie, including early widespread distribution of disease-associated prion protein (PrP d ) in lymphoid tissues, with later involvement of central nervous system (CNS) and peripheral tissues. This distribution likely contributes to apparent efficiency of horizontal transmission and, in this, is similar to scrapie and differs from BSE. Clinical features and lesions of CWD are qualitatively similar to the other animal TSEs. Microscopically, marked spongiform lesions occur in the central nervous system (CNS) after a prolonged incubation period and variable course of clinical disease. During incubation, PrP d can be identified in tissues by antibody-based detection systems. Although CWD can be transmitted by intracerebral inoculation to cattle, sheep, and goats, ongoing studies have not demonstrated that domestic livestock are susceptible via oral exposure, the presumed natural route of exposure to TSEs. Surveillance efforts for CWD in captive and free-ranging cervids will continue in concert with similar activities for scrapie and BSE. Eradication of CWD in farmed cervids is the goal of state, federal, and industry programs, but eradication of CWD from free-ranging populations of cervids is unlikely with currently available management techniques.Key words: Chronic wasting disease; elk; mule deer; prion disease; transmissible spongiform encephalopathy; white-tailed deer.The transmissible spongiform encephalopathies (TSEs) are unusual infectious diseases of animals and humans. The TSEs, including chronic wasting disease (CWD), are designated prion diseases because of their association with aberrantly refolded isoforms of the prion protein, a normal cellular glycoprotein (PrP C ). 120 CWD-associated prion protein (PrP CWD or PrP d ) 82 is widespread in the lymphoid tissues and the CNS from early in the incubation phase until death. 98,132,137 Scrapie, the first TSE identified, was the focus of considerable research and even controversy concerning its origin and nature (genetic versus infectious) for many years. 2,114,115 However, it was the recognition that prion diseases were transmissible and affected humans as well as animals that stimulated much of the current scientific interest in the nature of these diseases.Scrapie has been recognized for hundreds of years, transmissible mink encephalopathy (TME) for more than 50 years, CWD for more than 30 years, and bovine spongiform encephalopathy (BSE) for fewer than 20 years. Although CWD is now well known, it was just a few years ago considered an obscure disease of mule deer (Odocoileus hemionus) and elk (Cervus elaphus nelso...

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“…This finding suggested to the authors that vasopressin might accompany the neurophysin and cause release of adrenocortico trophic hormone. This provides a possible explanation for the adrenal cortical hypertrophy that had been noted previously (Beck et al, 1964).…”

Section: Discussionmentioning

confidence: 53%

“…In histological studies of scrapie-infected sheep brain, Beck et al (1964) demonstrated severe bilateral symmetrical degeneration in the hyopthalamo-neurohypophysial system with loss of cell bodies in the supraoptic nuclei and the paraventricular nuclei. Similar lesions were also present in the cerebellum, especially in the flocculo-nodular lobe, and in its afferent motor system, to which motor dysfunction may be attributed.…”

Section: Discussionmentioning

confidence: 99%

Scrapie-induced Alterations in Glucose Tolerance in Mice

Carp

Kim²,

Callahan³

1989

Journal of General Virology

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SUMMARYCertain scrapie strains cause obesity in several strains of mice. The potential association between obesity and altered glucose tolerance was assessed by monitoring body weight and glucose tolerance throughout the incubation period in scrapie strainmouse strain combinations that do and do not produce obesity. Virtually all obese mice showed reduced glucose tolerance as shown by significantly higher blood glucose levels 2 h after a glucose overload. Mice injected with a scrapie strain that did not cause obesity showed normal tolerance. The scrapie infectivity titre of the pancreas of obese mice clinically affected with scrapie was very low. Adrenalectomy prevented both the increase in weight and aberrant glucose tolerance but had no other effect on the course of the disease. Following increasing dilution of the inoculum, the increase in body weight and the development of aberrant glucose tolerance reached an end-point that was similar to that of scrapie infectivity. The system described provides an inducible model of obesity with altered glucose tolerance.

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Degeneration of the Cerebellar and Hypothalamo Neurohypophysial Systems in Sheep With Scrapie; And Its Relationship to Human System Degenerations

Cited by 107 publications

References 0 publications

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Naturally occurring scrapie is associated with a lower CBG binding capacity in ewes

Chronic Wasting Disease

Scrapie-induced Alterations in Glucose Tolerance in Mice

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