The degree of astrocyte activation is predictive of the incubation time to prion disease
Date
2021-05-12Journal
Acta Neuropathologica CommunicationsPublisher
Springer NatureType
Article
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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 diseasesNeuroinflammation
Prion
Prion diseases
Prion strains
Reactive astrocytes
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http://hdl.handle.net/10713/15661ae974a485f413a2113503eed53cd6c53
10.1186/s40478-021-01192-9
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