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• W1975998453 endingPage "e1003002" @default.
• W1975998453 startingPage "e1003002" @default.
• W1975998453 abstract "Prion diseases typically have long pre-clinical incubation periods during which time the infectious prion particle and infectivity steadily propagate in the brain. Abnormal neuritic sprouting and synaptic deficits are apparent during pre-clinical disease, however, gross neuronal loss is not detected until the onset of the clinical phase. The molecular events that accompany early neuronal damage and ultimately conclude with neuronal death remain obscure. In this study, we used laser capture microdissection to isolate hippocampal CA1 neurons and determined their pre-clinical transcriptional response during infection. We found that gene expression within these neurons is dynamic and characterized by distinct phases of activity. We found that a major cluster of genes is altered during pre-clinical disease after which expression either returns to basal levels, or alternatively undergoes a direct reversal during clinical disease. Strikingly, we show that this cluster contains a signature highly reminiscent of synaptic N-methyl-D-aspartic acid (NMDA) receptor signaling and the activation of neuroprotective pathways. Additionally, genes involved in neuronal projection and dendrite development were also altered throughout the disease, culminating in a general decline of gene expression for synaptic proteins. Similarly, deregulated miRNAs such as miR-132-3p, miR-124a-3p, miR-16-5p, miR-26a-5p, miR-29a-3p and miR-140-5p follow concomitant patterns of expression. This is the first in depth genomic study describing the pre-clinical response of hippocampal neurons to early prion replication. Our findings suggest that prion replication results in the persistent stimulation of a programmed response that is mediated, at least in part, by synaptic NMDA receptor activity that initially promotes cell survival and neurite remodelling. However, this response is terminated prior to the onset of clinical symptoms in the infected hippocampus, seemingly pointing to a critical juncture in the disease. Manipulation of these early neuroprotective pathways may redress the balance between degeneration and survival, providing a potential inroad for treatment." @default.
• W1975998453 created "2016-06-24" @default.
• W1975998453 creator A5002344673 @default.
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• W1975998453 date "2012-11-08" @default.
• W1975998453 modified "2023-10-15" @default.
• W1975998453 title "Early Mechanisms of Pathobiology Are Revealed by Transcriptional Temporal Dynamics in Hippocampal CA1 Neurons of Prion Infected Mice" @default.
• W1975998453 cites W144423133 @default.
• W1975998453 cites W1480120703 @default.
• W1975998453 cites W1530155692 @default.
• W1975998453 cites W1545554770 @default.
• W1975998453 cites W1563004998 @default.
• W1975998453 cites W1588326306 @default.
• W1975998453 cites W1604221682 @default.
• W1975998453 cites W1616958874 @default.
• W1975998453 cites W1764898023 @default.
• W1975998453 cites W1867953867 @default.
• W1975998453 cites W1897865160 @default.
• W1975998453 cites W1946755838 @default.
• W1975998453 cites W1964848350 @default.
• W1975998453 cites W1965115912 @default.
• W1975998453 cites W1966658105 @default.
• W1975998453 cites W1975100045 @default.
• W1975998453 cites W1977645267 @default.
• W1975998453 cites W1978044509 @default.
• W1975998453 cites W1978677736 @default.
• W1975998453 cites W1980269624 @default.
• W1975998453 cites W1985384585 @default.
• W1975998453 cites W1985527563 @default.
• W1975998453 cites W1985670883 @default.
• W1975998453 cites W1986660339 @default.
• W1975998453 cites W1989177998 @default.
• W1975998453 cites W1990586782 @default.
• W1975998453 cites W1991544505 @default.
• W1975998453 cites W1992187858 @default.
• W1975998453 cites W1993220836 @default.
• W1975998453 cites W1993781471 @default.
• W1975998453 cites W1994142447 @default.
• W1975998453 cites W1995550632 @default.
• W1975998453 cites W1996077375 @default.
• W1975998453 cites W1996887338 @default.
• W1975998453 cites W1997140657 @default.
• W1975998453 cites W1997282555 @default.
• W1975998453 cites W1997659400 @default.
• W1975998453 cites W1999750033 @default.
• W1975998453 cites W2002500198 @default.
• W1975998453 cites W2005816735 @default.
• W1975998453 cites W2005972504 @default.
• W1975998453 cites W2007804566 @default.
• W1975998453 cites W2008004502 @default.
• W1975998453 cites W2008481758 @default.
• W1975998453 cites W2008934254 @default.
• W1975998453 cites W2011875417 @default.
• W1975998453 cites W2012491213 @default.
• W1975998453 cites W2014924970 @default.
• W1975998453 cites W2015205234 @default.
• W1975998453 cites W2015269797 @default.
• W1975998453 cites W2021071726 @default.
• W1975998453 cites W2021719065 @default.
• W1975998453 cites W2022196959 @default.
• W1975998453 cites W2026483968 @default.
• W1975998453 cites W2026534774 @default.
• W1975998453 cites W2026570544 @default.
• W1975998453 cites W2026686516 @default.
• W1975998453 cites W2029161769 @default.
• W1975998453 cites W2029443323 @default.
• W1975998453 cites W2034631640 @default.
• W1975998453 cites W2035631829 @default.
• W1975998453 cites W2037013087 @default.
• W1975998453 cites W2037038958 @default.
• W1975998453 cites W2037256374 @default.
• W1975998453 cites W2037491812 @default.
• W1975998453 cites W2038043012 @default.
• W1975998453 cites W2038874091 @default.
• W1975998453 cites W2039141906 @default.
• W1975998453 cites W2039456360 @default.
• W1975998453 cites W2042651745 @default.
• W1975998453 cites W2042978244 @default.
• W1975998453 cites W2045262404 @default.
• W1975998453 cites W2046969024 @default.
• W1975998453 cites W2047716189 @default.
• W1975998453 cites W2047884170 @default.
• W1975998453 cites W2048516415 @default.
• W1975998453 cites W2049103748 @default.
• W1975998453 cites W2050331820 @default.
• W1975998453 cites W2052908582 @default.
• W1975998453 cites W2054504521 @default.
• W1975998453 cites W2057231053 @default.
• W1975998453 cites W2057436796 @default.
• W1975998453 cites W2058085266 @default.
• W1975998453 cites W2059073003 @default.

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