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    The degree of astrocyte activation is predictive of the incubation time to prion disease

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    Author
    Makarava, Natallia
    Mychko, Olga
    Chang, Jennifer Chen-Yu
    Molesworth, Kara
    Baskakov, Ilia V
    Date
    2021-05-12
    Journal
    Acta Neuropathologica Communications
    Publisher
    Springer Nature
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://doi.org/10.1186/s40478-021-01192-9
    Abstract
    In 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.
    Keyword
    Neurodegenerative diseases
    Neuroinflammation
    Prion
    Prion diseases
    Prion strains
    Reactive astrocytes
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/15661
    ae974a485f413a2113503eed53cd6c53
    10.1186/s40478-021-01192-9
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