Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time
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Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time. / Muth, Christiane; Schröck, Katharina; Madore, Charlotte; Hartmann, Kristin; Fanek, Zain; Butovsky, Oleg; Glatzel, Markus; Krasemann, Susanne.
in: BRAIN PATHOL, Jahrgang 27, Nr. 5, 09.2017, S. 590-602.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Activation of microglia by retroviral infection correlates with transient clearance of prions from the brain but does not change incubation time
AU - Muth, Christiane
AU - Schröck, Katharina
AU - Madore, Charlotte
AU - Hartmann, Kristin
AU - Fanek, Zain
AU - Butovsky, Oleg
AU - Glatzel, Markus
AU - Krasemann, Susanne
N1 - © 2016 International Society of Neuropathology.
PY - 2017/9
Y1 - 2017/9
N2 - Prion diseases are fatal transmissible diseases, where conversion of the endogenous prion protein (PrP(C) ) into a misfolded isoform (PrP(Sc) ) leads to neurodegeneration. Microglia, the immune cells of the brain, are activated in neurodegenerative disorders including prion diseases; however, their impact on prion disease pathophysiology is unclear with both beneficial PrP(Sc) -clearing and detrimental potentially neurotoxic effects. Moreover, monocytes entering the brain from the periphery during disease course might add to disease pathophysiology. Here, the degree of microglia activation in the brain of prion infected mice with and without an additional intraperitoneal retrovirus infection was studied. Peripheral murine retrovirus infection leads to activation of parenchymal microglia without recruitment of monocytes. This activation correlated with transient clearance or delay in accumulation of infectious prions specifically from the brain at early time points in the diseases course. Microglia expression profiling showed upregulation of genes involved in protein degradation coinciding with prion clearance. This enforces a concept where microglia act beneficial in prion disease if adequately activated. Once microglia activation has ceased, prion disease reemerges leading to disease kinetics undistinguishable from the situation in prion-only infected mice. This might be caused by the loss of microglial homeostatic function at clinical prion disease.
AB - Prion diseases are fatal transmissible diseases, where conversion of the endogenous prion protein (PrP(C) ) into a misfolded isoform (PrP(Sc) ) leads to neurodegeneration. Microglia, the immune cells of the brain, are activated in neurodegenerative disorders including prion diseases; however, their impact on prion disease pathophysiology is unclear with both beneficial PrP(Sc) -clearing and detrimental potentially neurotoxic effects. Moreover, monocytes entering the brain from the periphery during disease course might add to disease pathophysiology. Here, the degree of microglia activation in the brain of prion infected mice with and without an additional intraperitoneal retrovirus infection was studied. Peripheral murine retrovirus infection leads to activation of parenchymal microglia without recruitment of monocytes. This activation correlated with transient clearance or delay in accumulation of infectious prions specifically from the brain at early time points in the diseases course. Microglia expression profiling showed upregulation of genes involved in protein degradation coinciding with prion clearance. This enforces a concept where microglia act beneficial in prion disease if adequately activated. Once microglia activation has ceased, prion disease reemerges leading to disease kinetics undistinguishable from the situation in prion-only infected mice. This might be caused by the loss of microglial homeostatic function at clinical prion disease.
U2 - 10.1111/bpa.12441
DO - 10.1111/bpa.12441
M3 - SCORING: Journal article
C2 - 27558169
VL - 27
SP - 590
EP - 602
JO - BRAIN PATHOL
JF - BRAIN PATHOL
SN - 1015-6305
IS - 5
ER -