Fig. 6 | Nature Communications

Fig. 6

From: Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice

Fig. 6

TNF-α mediates microglial activation, ZIKV-induced synapse and memory impairment. Adult Swiss mice received an i.c.v. infusion of 105 PFU ZIKV or mock medium and were treated (or not) with Infliximab (Inflix; 0.2 μg/day, from 2 to 6 dpi, i.c.v.). ac Representative images of Iba-1 immunolabeling in hippocampi of mock-infused (a), ZIKV-infected mice treated with vehicle (b), or ZIKV-infected mice treated with Infliximab (c) at 10 dpi. Scale bar = 200 μm, inset scale bar = 50 μm. d, e Integrated Iba-1 optical density (d) and number of Iba-1-positive cells (e) in the hippocampus (d F(2,9) = 4.629, *p = 0.043; e F(2,9) = 5.254, *p < 0.0327, one-way ANOVA followed by Bonferroni, N = 4 mice/group). fh Representative images of the CA3 hippocampal region of mock-infused (f), ZIKV-infected mice treated with vehicle (g), or ZIKV-infected mice treated with Infliximab (h) immunolabeled for synaptophysin (SYP, green) and Homer1 (red). Scale bar = 25 μm, inset scale bar = 5 μm. ik SYP (i), Homer1 (j), and colocalized SYP/Homer1 puncta (k). (i F(2,9) = 4.917, *p = 0.0364, k F(2,9) = 5.682, *p = 0.0166, one-way ANOVA followed by Bonferroni’s; N = 4 mice/group). l Mice were tested in the NOR test at 6 dpi (l: t = 2.364 *p = 0.0456 for mock/Veh, t = 2.688 *p = 0.0276 for mock/Inflix, t = 2.310 *p = 0.0497 for ZIKV/Inflix; one-sample Student’s t-test compared to the chance level of 50%; N = 10 (ZIKV) and 9 (other groups); data represent one of two independent experiments). mp Infliximab prevents ZIKV-induced impairment in LTP in dorsal hippocampal CA3 area. m Means ± SEM of slopes of field excitatory post-synaptic potentials (fEPSPs) evoked in CA3 by mossy fiber stimulation, before and after high-frequency stimulation (HFS), in slices from mock- or ZIKV-infused mice treated with infliximab. n Representative fEPSPs before (black) and 35–40 min after (red) HFS. o Average fEPSP slopes 35–40 min post-HFS. p Baseline paired-pulse amplitude ratios. (N = 10 slices from 7 mock-infused and 9 slices from 6 ZIKV-infected mice). Bars represent means ± SEM. Symbols correspond to individual mice (al) or individual slices (op). Source data (panels de, ip) are provided as Source Data File

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