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dc.contributor.authorMakarava, Natallia
dc.contributor.authorMychko, Olga
dc.contributor.authorChang, Jennifer Chen-Yu
dc.contributor.authorMolesworth, Kara
dc.contributor.authorBaskakov, Ilia V
dc.date.accessioned2021-05-17T14:41:20Z
dc.date.available2021-05-17T14:41:20Z
dc.date.issued2021-05-12
dc.identifier.urihttp://hdl.handle.net/10713/15661
dc.description.abstractIn neurodegenerative diseases including Alzheimer's, Parkinson's and prion diseases, astrocytes acquire disease-associated reactive phenotypes. With growing appreciation of their role in chronic neurodegeneration, the questions whether astrocytes lose their ability to perform homeostatic functions in the reactive states and whether the reactive phenotypes are neurotoxic or neuroprotective remain unsettled. The current work examined region-specific changes in expression of genes, which report on astrocyte physiological functions and their reactive states, in C57Black/6J mice challenged with four prion strains via two inoculation routes. Unexpectedly, strong reverse correlation between the incubation time to the diseases and the degree of astrocyte activation along with disturbance in functional pathways was observed. The animal groups with the most severe astrocyte response and degree of activation showed the most rapid disease progression. The degree of activation tightly intertwined with the global transformation of the homeostatic state, characterized by disturbances in multiple gene sets responsible for normal physiological functions producing a neurotoxic, reactive phenotype as a net result. The neurotoxic reactive phenotype exhibited a universal gene signature regardless of the prion strain. The current work suggests that the degree of astrocyte activation along with the disturbance in their physiological pathways contribute to the faster progression of disease and perhaps even drive prion pathogenesis.en_US
dc.description.urihttps://doi.org/10.1186/s40478-021-01192-9en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofActa Neuropathologica Communicationsen_US
dc.subjectNeurodegenerative diseasesen_US
dc.subjectNeuroinflammationen_US
dc.subjectPrionen_US
dc.subjectPrion diseasesen_US
dc.subjectPrion strainsen_US
dc.subjectReactive astrocytesen_US
dc.titleThe degree of astrocyte activation is predictive of the incubation time to prion diseaseen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s40478-021-01192-9
dc.identifier.pmid33980286
dc.source.volume9
dc.source.issue1
dc.source.beginpage87
dc.source.endpage
dc.source.countryUnited States
dc.source.countryEngland


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