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. Author manuscript; available in PMC: 2015 Aug 12.
Published in final edited form as: Nature. 2015 Jan 14;518(7538):236–239. doi: 10.1038/nature14142

Figure 3. Early cooling induces RBM3 over-expression and is neuroprotective in prion-infected mice.

Figure 3

a) Cooling at 3 and 4 w.p.i. resulted in sustained high levels of RBM3 in hippocampus for several weeks (n= 3-8 mice per time point) causing b) marked protection of synapse number at 7, 8 and 9 w.p.i. (62 images from 2 mice per time point). Scale bar = 1μm. c) Early cooling maintained synaptic transmission (n= 4-8 cells from 2 mice per time point; representative raw traces of evoked EPSCs are shown) and d) prevented decline in burrowing behaviour and loss of novel object recognition memory, expressed as ratio of exploratory preference (n ≥10 mice per group) in contrast to un-cooled mice. e) Haematoxylin and eosin stained sections show striking reduction in hippocampal spongiosis and protection of CA1 neurons (bar chart) in cooled mice that is abolished by RBM3 knockdown (n = 4-6 animals per treatment, except LV-shRNA-RBM3: n = 2). Scale bar = 50μm. One-way ANOVA, Brown-Forsythe test with Tukey’s post hoc analysis for multiple comparisons was used in d and e. f) Early cooling significantly prolonged survival, but this was abolished by knockdown of RBM3 (n = 31 cooled mice; n = 17 not cooled; n = 10 cooled + RNAi of RBM3). Mann-Whitney U test. *p < 0.05; **p< 0.01; ***p < 0.001. Student’s t-test two tails was used unless otherwise stated. All data in bar charts are mean ± s.e.m.