scholarly journals Prion type 2 selection in sporadic Creutzfeldt–Jakob disease affecting peripheral ganglia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Hofmann ◽  
Arne Wrede ◽  
Wiebke M. Jürgens-Wemheuer ◽  
Walter J. Schulz-Schaeffer
Keyword(s):  
Central Nervous System ◽  
Prion Protein ◽  
Trigeminal Ganglion ◽  
Dorsal Root ◽  
Pathological Changes ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Dependent Property

AbstractIn sporadic Creutzfeldt–Jakob disease (sCJD), the pathological changes appear to be restricted to the central nervous system. Only involvement of the trigeminal ganglion is widely accepted. The present study systematically examined the involvement of peripheral ganglia in sCJD utilizing the currently most sensitive technique for detecting prions in tissue morphologically. The trigeminal, nodose, stellate, and celiac ganglia, as well as ganglia of the cervical, thoracic and lumbar sympathetic trunk of 40 patients were analyzed with the paraffin-embedded tissue (PET)-blot method. Apart from the trigeminal ganglion, which contained protein aggregates in five of 19 prion type 1 patients, evidence of prion protein aggregation was only found in patients associated with type 2 prions. With the PET-blot, aggregates of prion protein type 2 were found in all trigeminal (17/17), in some nodose (5 of 7) and thoracic (3 of 6) ganglia, as well as in a few celiac (4 of 19) and lumbar (1 of 5) ganglia of sCJD patients. Whereas aggregates of both prion types may spread to dorsal root ganglia, more CNS-distant ganglia seem to be only involved in patients accumulating prion type 2. Whether the prion type association is due to selection by prion type-dependent replication, or due to a prion type-dependent property of axonal spread remains to be resolved in further studies.

scholarly journals Neuroinvasion in Prion Diseases: The Roles of Ascending Neural Infection and Blood Dissemination

2010 ◽  
Vol 2010 ◽  
pp. 1-16 ◽  
Author(s):  
Sílvia Sisó ◽  
Lorenzo González ◽  
Martin Jeffrey
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prion Protein ◽  
Prion Diseases ◽  
Autonomic Nerves ◽  
Peripheral Organs ◽  
Prion Strains ◽  
New Variant ◽  
Jakob Disease ◽  
The Central Nervous System

Prion disorders are infectious, neurodegenerative diseases that affect humans and animals. Susceptibility to some prion diseases such as kuru or the new variant of Creutzfeldt-Jakob disease in humans and scrapie in sheep and goats is influenced by polymorphisms of the coding region of the prion protein gene, while other prion disorders such as fatal familial insomnia, familial Creutzfeldt-Jakob disease, or Gerstmann-Straussler-Scheinker disease in humans have an underlying inherited genetic basis. Several prion strains have been demonstrated experimentally in rodents and sheep. The progression and pathogenesis of disease is influenced by both genetic differences in the prion protein and prion strain. Some prion diseases only affect the central nervous system whereas others involve the peripheral organs prior to neuroinvasion. Many experiments undertaken in different species and using different prion strains have postulated common pathways of neuroinvasion. It is suggested that prions access the autonomic nerves innervating peripheral organs and tissues to finally reach the central nervous system. We review here published data supporting this view and additional data suggesting that neuroinvasion may concurrently or independently involve the blood vascular system.

Development and regeneration in the central nervous system

1990 ◽  
Vol 327 (1239) ◽  
pp. 127-143 ◽  
Keyword(s):  
Stem Cells ◽  
Central Nervous System ◽  
Nervous System ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Cell Types ◽  
The Central Nervous System

As part of our attempts to understand principles that underly organism development, we have been studying the development of the rat optic nerve. This simple tissue is composed of three glial cell types derived from two distinct cellular lineages. Type-1 astrocytes appear to be derived from a monopotential neuroepithelial precursor, whereas type-2 astrocytes and oligodendrocytes are derived from a common oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell. Type-1 astrocytes modulate division and differentiation of O-2A progenitor cells through secretion of platelet-derived growth factor, and can themselves be stimulated to divide by peptide mitogens and through stimulation of neurotransmitter receptors. In vitro analysis indicates that many dividing O-2A progenitors derived from optic nerves of perinatal rats differentiate symmetrically and clonally to give rise to oligodendrocytes, or can be induced to differentiate into type-2 astrocytes. O-2A perinatal progenitors can also differentiate to form a further O-2A lineage cell, the O-2A adult progenitor, which has properties specialized for the physiological requirements of the adult nervous system. In particular, O-2A adult progenitors have many of the features of stem cells, in that they divide slowly and asymmetrically and appear to have the capacity for extended self-renewal. The apparent derivation of a slowly and asymmetrically dividing cell, with properties appropriate for homeostatic maintenance of existing populations in the mature animal, from a rapidly dividing cell with properties suitable for the rapid population and myelination of central nervous system (CNS) axon tracts during early development, offers novel and unexpected insights into the possible origin of self-renewing stem cells and also into the role that generation of stem cells may play in helping to terminate the explosive growth of embryogenesis. Moreover, the properties of O-2A adult progenitor cells are consistent with, and may explain, the failure of successful myelin repair in conditions such as multiple sclerosis, and thus seem to provide a cellular biological basis for understanding one of the key features of an important human disease.

scholarly journals Postmortem Quantitative Analysis of Prion Seeding Activity in the Digestive System

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4601 ◽  
Author(s):  
Katsuya Satoh ◽  
Takayuki Fuse ◽  
Toshiaki Nonaka ◽  
Trong Dong ◽  
Masaki Takao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Quantitative Analysis ◽  
Prion Protein ◽  
Neurodegenerative Disorders ◽  
Digestive System ◽  
Prion Diseases ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Almost All

Human prion diseases are neurodegenerative disorders caused by prion protein. Although infectivity was historically detected only in the central nervous system and lymphoreticular tissues of patients with sporadic Creutzfeldt-Jakob disease, recent reports suggest that the seeding activity of Creutzfeldt-Jakob disease prions accumulates in various non-neuronal organs including the liver, kidney, and skin. Therefore, we reanalyzed autopsy samples collected from patients with sporadic and genetic human prion diseases and found that seeding activity exists in almost all digestive organs. Unexpectedly, activity in the esophagus reached a level of prion seeding activity close to that in the central nervous system in some CJD patients, indicating that the safety of endoscopic examinations should be reconsidered.

scholarly journals Prion Strain Characterization of a Novel Subtype of Creutzfeldt-Jakob Disease

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Roberta Galeno ◽  
Michele Angelo Di Bari ◽  
Romolo Nonno ◽  
Franco Cardone ◽  
Marco Sbriccoli ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Prion Protein ◽  
Protein Gene ◽  
Prion Protein Gene ◽  
Prion Strain ◽  
Bank Voles ◽  
Jakob Disease ◽  
Codon 129

ABSTRACT In 2007, we reported a patient with an atypical form of Creutzfeldt-Jakob disease (CJD) heterozygous for methionine-valine (MV) at codon 129 who showed a novel pathological prion protein (PrPTSE) conformation with an atypical glycoform (AG) profile and intraneuronal PrP deposition. In the present study, we further characterize the conformational properties of this pathological prion protein (PrPTSE MVAG), showing that PrPTSE MVAG is composed of multiple conformers with biochemical properties distinct from those of PrPTSE type 1 and type 2 of MV sporadic CJD (sCJD). Experimental transmission of CJD-MVAG to bank voles and gene-targeted transgenic mice carrying the human prion protein gene (TgHu mice) showed unique transmission rates, survival times, neuropathological changes, PrPTSE deposition patterns, and PrPTSE glycotypes that are distinct from those of sCJD-MV1 and sCJD-MV2. These biochemical and experimental data suggest the presence of a novel prion strain in CJD-MVAG. IMPORTANCE Sporadic Creutzfeldt-Jakob disease is caused by the misfolding of the cellular prion protein, which assumes two different major conformations (type 1 and type 2) and, together with the methionine/valine polymorphic codon 129 of the prion protein gene, contribute to the occurrence of distinct clinical-pathological phenotypes. Inoculation in laboratory rodents of brain tissues from the six possible combinations of pathological prion protein types with codon 129 genotypes results in the identification of 3 or 4 strains of prions. We report on the identification of a novel strain of Creutzfeldt-Jakob disease isolated from a patient who carried an abnormally glycosylated pathological prion protein. This novel strain has unique biochemical characteristics, does not transmit to humanized transgenic mice, and shows exclusive transmission properties in bank voles. The identification of a novel human prion strain improves our understanding of the pathogenesis of the disease and of possible mechanisms of prion transmission.

Diagnosis and Management of Narcolepsy

2017 ◽  
Vol 37 (04) ◽  
pp. 446-460 ◽  
Author(s):  
Logan Schneider ◽  
Emmanuel Mignot
Keyword(s):  
Central Nervous System ◽  
Respiratory Infections ◽  
Genetic Studies ◽  
Upper Respiratory Infections ◽  
Idiopathic Hypersomnia ◽  
Atypical Manifestations ◽  
The Central Nervous System ◽  
Upper Respiratory

AbstractType 1 narcolepsy is caused by deficient hypocretin signaling in the central nervous system (CNS), and is distinct from other primary CNS hypersomnias, which seem to lay along a spectrum from type 2 narcolepsy to idiopathic hypersomnia. There appears to be a strong autoimmune diathesis to the development of type 1 narcolepsy, as evidenced by the near universal presence of HLA-DQB1*06:02 in patients. Growing knowledge of the immunogenetic basis of the disease is supported by genetic studies and seasonal variation of type 1 narcolepsy incidence following winter upper respiratory infections (e.g., strep throat and influenza). Despite improved diagnostic accuracy of adding cerebrospinal fluid hypocretin measurement to the traditional workup, recognition of the disorder remains limited by its moderate prevalence and atypical manifestations in different ethnic groups. Treatments are currently symptom-based, and have been extended to other hypersomnias with mixed results.

Neurofibromatosis Type 1 and Type 2: review of the central nervous system and related structures

1997 ◽  
Vol 19 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Yuichi Inoue ◽  
Yutaka Nemoto ◽  
Takahiko Tashiro ◽  
Keiko Nakayama ◽  
Tetsuo Nakayama ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurofibromatosis Type 1 ◽  
Neurofibromatosis Type ◽  
The Central Nervous System

scholarly journals Update in the CNS Response to Hypoglycemia

2012 ◽  
Vol 97 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Rory J. McCrimmon
Keyword(s):  
Type 2 Diabetes ◽  
Central Nervous System ◽  
Type 1 Diabetes ◽  
Nervous System ◽  
Animal Studies ◽  
Human Subjects ◽  
Diabetes Research ◽  
The Central Nervous System

Hypoglycemia remains a major clinical issue in the management of people with type 1 and type 2 diabetes. Research in basic science is only beginning to unravel the mechanisms that: 1) underpin the detection of hypoglycemia and initiation of a counterregulatory defense response; and 2) contribute to the development of defective counterregulation in both type 1 and type 2 diabetes, particularly after prior exposure to repeated hypoglycemia. In animal studies, the central nervous system has emerged as key to these processes. However, bench-based research needs to be translated through studies in human subjects as a first step to the future development of clinical intervention. This Update reviews studies published in the last 2 yr that examined the central nervous system effects of hypoglycemia in human subjects, largely through neuroimaging techniques, and compares these data with those obtained from animal studies and the implications for future therapies. Based on these studies, it is increasingly clear that our understanding of how the brain responds and adapts to recurrent hypoglycemia remains very limited. Current therapies have provided little evidence that they can prevent severe hypoglycemia or improve hypoglycemia awareness in type 1 diabetes. There remains an urgent need to increase our understanding of how and why defective counterregulation develops in type 1 diabetes in order for novel therapeutic interventions to be developed and tested.

scholarly journals Non-Oncological Neuroradiological Manifestations in NF1 and Their Clinical Implications

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1831
Author(s):  
Camilla Russo ◽  
Carmela Russo ◽  
Daniele Cascone ◽  
Federica Mazio ◽  
Claudia Santoro ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Structural Organization ◽  
Neurofibromatosis Type ◽  
Review Article ◽  
Tumor Suppressor Protein ◽  
Clinical Implications ◽  
Nf1 Gene ◽  
The Central Nervous System

Neurofibromatosis type 1 (NF1), the most frequent phakomatosis and one of the most common inherited tumor predisposition syndromes, is characterized by several manifestations that pervasively involve central and peripheral nervous system structures. The disorder is due to mutations in the NF1 gene, which encodes for the ubiquitous tumor suppressor protein neurofibromin; neurofibromin is highly expressed in neural crest derived tissues, where it plays a crucial role in regulating cell proliferation, differentiation, and structural organization. This review article aims to provide an overview on NF1 non-neoplastic manifestations of neuroradiological interest, involving both the central nervous system and spine. We also briefly review the most recent MRI functional findings in NF1.

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