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dc.contributor.authorPaquet, Claire*
dc.contributor.authorBose, Anindita*
dc.contributor.authorPolivka, Marc*
dc.contributor.authorPeoc'h, Katell*
dc.contributor.authorBrouland, Jean Philippe*
dc.contributor.authorKeohane, Catherine*
dc.contributor.authorHugon, Jacques*
dc.contributor.authorGray, Françoise*
dc.date.accessioned2012-01-10T12:50:05Z
dc.date.available2012-01-10T12:50:05Z
dc.date.issued2009-02
dc.identifier.citationNeuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease. 2009, 68 (2):190-8 J. Neuropathol. Exp. Neurol.en
dc.identifier.issn0022-3069
dc.identifier.pmid19151623
dc.identifier.doi10.1097/NEN.0b013e318196cd7c
dc.identifier.urihttp://hdl.handle.net/10147/201228
dc.descriptionA comparative study of the craniofacial complex in men with an extra X chromosome, and normal male and female individuals was carried out using cephalometric radiography. The anterior cranial base, anterior and posterior facial height, maxillary base and ascending ramus were found to be significantly decreased in men with Klinefelter syndrome when compared to the male control group. Significant differences in the lengths of mandibular base and posterior cranial base were not found. When compared to the female control, all structures examined were significantly increased, except for the maxillary base.en
dc.description.abstractThe mechanisms of neuronal apoptosis in Creutzfeldt-Jakob disease (CJD) and their relationship to accumulated prion protein (PrP) are unclear. A recent cell culture study showed that intracytoplasmic PrP may induce phosphorylated RNA-dependent protein kinase (PKR(p))-mediated cell stress. The double-stranded RNA protein kinase PKR is a proapoptotic and stress kinase that accumulates in degenerating neurons in Alzheimer disease. To determine whether neuronal apoptosis in human CJD is associated with activation of the PKR(p) signaling pathway, we assessed in situ end labeling and immunocytochemistry for PrP, glial fibrillary acidic protein, CD68, activated caspase 3, and phosphorylated PKR (Thr451) in samples of frontal, occipital, and temporal cortex, striatum, and cerebellum from 6 patients with sporadic CJD and 5 controls. Neuronal immunostaining for activated PKR was found in all CJD cases. The most staining was in nuclei and, in contrast to findings in Alzheimer disease, cytoplasmic labeling was not detected. Both the number and distribution of PKR(p)-positive neurons correlated closely with the extent of neuronal apoptosis, spongiosis, astrocytosis, and microglial activation and with the phenotype and disease severity. There was no correlation with the type, topography, or amount of extracellular PrP deposits. These findings suggest that neuronal apoptosis in human CJD may result from PKR(p)-mediated cell stress and are consistent with recent studies supporting a pathogenic role for intracellular or transmembrane PrP.
dc.language.isoenen
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshApoptosis
dc.subject.meshBrain
dc.subject.meshCaspase 3
dc.subject.meshCell Nucleus
dc.subject.meshCreutzfeldt-Jakob Syndrome
dc.subject.meshFemale
dc.subject.meshGlial Fibrillary Acidic Protein
dc.subject.meshGliosis
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshIn Situ Nick-End Labeling
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshNerve Degeneration
dc.subject.meshNeurons
dc.subject.meshPhosphorylation
dc.subject.meshPrions
dc.subject.meshStress, Physiological
dc.subject.mesheIF-2 Kinase
dc.titleNeuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease.en
dc.typeArticleen
dc.contributor.departmentService Central d'Anatomie et de Cytologie Pathologiques, APHP, Hôpital Lariboisière-Université Paris VII, France.en
dc.identifier.journalJournal of neuropathology and experimental neurologyen
dc.description.provinceMunster
html.description.abstractThe mechanisms of neuronal apoptosis in Creutzfeldt-Jakob disease (CJD) and their relationship to accumulated prion protein (PrP) are unclear. A recent cell culture study showed that intracytoplasmic PrP may induce phosphorylated RNA-dependent protein kinase (PKR(p))-mediated cell stress. The double-stranded RNA protein kinase PKR is a proapoptotic and stress kinase that accumulates in degenerating neurons in Alzheimer disease. To determine whether neuronal apoptosis in human CJD is associated with activation of the PKR(p) signaling pathway, we assessed in situ end labeling and immunocytochemistry for PrP, glial fibrillary acidic protein, CD68, activated caspase 3, and phosphorylated PKR (Thr451) in samples of frontal, occipital, and temporal cortex, striatum, and cerebellum from 6 patients with sporadic CJD and 5 controls. Neuronal immunostaining for activated PKR was found in all CJD cases. The most staining was in nuclei and, in contrast to findings in Alzheimer disease, cytoplasmic labeling was not detected. Both the number and distribution of PKR(p)-positive neurons correlated closely with the extent of neuronal apoptosis, spongiosis, astrocytosis, and microglial activation and with the phenotype and disease severity. There was no correlation with the type, topography, or amount of extracellular PrP deposits. These findings suggest that neuronal apoptosis in human CJD may result from PKR(p)-mediated cell stress and are consistent with recent studies supporting a pathogenic role for intracellular or transmembrane PrP.


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