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• W1524635632 abstract "While prion infection ultimately involves the entire brain, it has long been thought that the abrupt clinical onset and rapid neurological decline in laboratory rodents relates to involvement of specific critical neuroanatomical target areas. The severity and type of clinical signs, together with the rapid progression, suggest the brainstem as a candidate location for such critical areas. In this study we aimed to correlate prion pathology with clinical phenotype in order to identify clinical target areas.We conducted a comprehensive survey of brainstem pathology in mice infected with two distinct prion strains, which produce different patterns of pathology, in mice overexpressing prion protein (with accelerated clinical onset) and in mice in which neuronal expression was reduced by gene targeting (which greatly delays clinical onset).We identified specific brainstem areas that are affected by prion pathology during the progression of the disease. In the early phase of disease the locus coeruleus, the nucleus of the solitary tract, and the pre-Bötzinger complex were affected by prion protein deposition. This was followed by involvement of the motor and autonomic centres of the brainstem.Neurodegeneration in the locus coeruleus, the nucleus of the solitary tract and the pre-Bötzinger complex predominated and corresponded to the manifestation of the clinical phenotype. Because of their fundamental role in controlling autonomic function and the overlap with clinical signs in sporadic Creutzfeldt-Jakob disease, we suggest that these nuclei represent key clinical target areas in prion diseases." @default.
• W1524635632 created "2016-06-24" @default.
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• W1524635632 date "2015-04-23" @default.
• W1524635632 modified "2023-09-27" @default.
• W1524635632 title "Identification of clinical target areas in the brainstem of prion-infected mice" @default.
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• W1524635632 doi "https://doi.org/10.1111/nan.12189" @default.
• W1524635632 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4949711" @default.
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• W1524635632 hasPublicationYear "2015" @default.
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