Neuronal Ndst1 depletion accelerates prion protein clearance and slows neurodegeneration in prion infection
Fig 2
Reducing neuronal HS sulfation prolongs survival and lessens plaque load in prion-affected mice.
(A) Schematic illustrates mCWD prion inoculation and tissue collection. (B) Survival curves for mCWD-infected SynCre- (n = 10) and SynCre+ mice (n = 15). (C) Representative images reveal mCWD prion plaques in the corpus callosum (CC) of SynCre- mice and within vessels of the velum interpositum (VI) and hippocampus (HP) of SynCre+ mice. Higher magnification depicted in right panels. Scale bars represent 500 μm (left) and 50 μm (right). (D) Pie charts show the plaque distribution in brain. VI and cerebellar (CB) aggregates were primarily vascular (meninges) (n = 6 SynCre- and 9 SynCre+ mice). S6 Table indicates the plaque number in each brain area. (E) Representative images of PrPSc immunolabelled plaques in CC. Scale bar = 50 μm. (F) Quantification of the plaque length (CC) (n = 33 and 38 plaques in SynCre- and SynCre+, respectively) (n = 4 mice per genotype). (G) Representative example of dual immunolabelled mCWD-infected brain sections for PrPSc and endothelial cells (CD31) (parenchymal plaques: corpus callosum; SynCre- vascular plaque: basal ganglia; SynCre+ vascular plaque: thalamus). Scale bar represents 50 μm. (H) Quantification of parenchymal (par) and vascular (vasc) plaques in cerebral cortex, septum, corpus callosum, hippocampus, thalamus, cerebral peduncle, hypothalamus, cerebellar peduncle, velum interpositum, cerebellum, and medulla. N = 6 SynCre- and 9 SynCre+ mice. *P< 0.05, **P< 0.01, ***P< 0.005, and ****P< 0.001, Log-rank (Mantel-Cox) test (panel B), unpaired two-tailed t-test with Bonferroni’s post test (panel F), and two-way ANOVA with Bonferroni’s post test (panel H). TH thalamus, BG: basal ganglia, and CT: cerebral cortex. Panel A created with BioRender.com.