Fig. 5 | Nature Communications

Fig. 5

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

Fig. 5

Microglia mediates ZIKV-induced memory impairment in mice. Adult mice received an i.c.v. infusion of 105 PFU ZIKV or mock medium. a, b Representative images of microglia (Iba-1 positive, red) engulfing pre-synaptic terminals immunolabeled for pre-synaptic marker synaptophysin (SYP, green) in the hippocampus of mock- (a) or ZIKV-infected mice (b) at 6 dpi. White arrows point to SYP-positive elements engulfed within microglia. Scale bar = 20 μm. c Quantification of microglia-SYP colocalization (t = 3.502, *p = 0.0128; N = 3 (mock) and 5 (ZIKV)). dn Mice were treated with minocycline (Mino; 50 mg/kg i.p., 3 times/week beginning one week prior to infection). df Representative images of Iba-1 immunoreactivity in hippocampi of mock- (d), ZIKV-infected (e), or minocycline-treated ZIKV-infected mice (f) mice at 10 dpi. Scale bar = 20 μm. g Iba-1 positive cells in mice hippocampi at 10 dpi. h Maximum-minimum Feret index from microglia in hippocampi of mice (g: F(2,10) = 3.986; *p = 0.005 mock vs ZIKV, p = 0.0145 mock vs ZIKV+Mino; h: F(2,10) = 3.960; *p < 0.0001 mock vs ZIKV and ZIKV vs. ZIKV+Mino, one-way ANOVA followed by Bonferroni). (N = 4 (mock), 4 (ZIKV), 5 (ZIKV+Mino)). i Mice were tested in the novel object recognition (NOR) test at 9 dpi (i: t = 2.736 *p = 0.0144 for mock; t = 2.578 *p = 0.0366 for ZIKV+Mino, one-sample Student’s t-test compared to 50% chance level; N = 8 (Mock), 8(ZIKV+Mino), and 10 (ZIKV); data represent one of two independent experiments). jn Minocycline prevents ZIKV-induced impaired LTP in dorsal hippocampal CA3 area. j 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 mice treated with minocycline. k Representative fEPSPs recorded before (black) and 35–40 min after (red) HFS. l Average fEPSP slopes 35–40 min post-HFS. m Baseline paired-pulse amplitude ratios. (N = 8 slices from 5 mock-infused and 10 slices from 7 ZIKV-infected mice). n TNF-α expression in hippocampi of mice at 10 dpi (F(2,12) = 2.538, *p = 0.0005 mock vs. ZIKV+Veh or ZIKV+Mino, one-way ANOVA followed by Bonferroni’s, N = 5 mice/group). Bars represent means ± SEM. Symbols represent individual mice (aI, n) or individual slices (lm). Source data from panels c, gn are provided as Source Data File

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