Skip to main content
. 2023 Feb 17;42(3):112189. doi: 10.1016/j.celrep.2023.112189

Figure 1.

Figure 1

Spike protein causes synapse damage and memory impairment in mice

(A) Mice received an i.c.v. infusion of 6.5 μg of SARS-CoV-2 Spike protein (Spike) or vehicle (Veh) and were evaluated at early (up to 7 days) or late time points (from 30–60 days) after infusion using behavioral and molecular approaches.

(B–E) Mice were tested in the NOR test at 6 days (B; t = 2.626, ∗p = 0.0304 for Veh; t = 3.218, ∗p = 0.0105 for Spike), 30 days (C; t = 5.099, ∗p = 0.0014 for Veh; t = 1.645, p = 0.1386 for Spike), 45 days (D; t = 5.122, ∗p = 0.0014 for Veh; t = 1.189, p = 0.2685 for Spike), or 60 days (E; t = 2.913, ∗p = 0.0195 for Veh; t = 2.560, ∗p = 0.0336 for Spike). One-sample Student’s t test compared with the chance level of 50% (n = 8–10 mice per group).

(F and G) Escape latency across 4 consecutive training trials (F) and time spent in the target quadrant during the probe trial (G) of the MWM test performed 45 days after Spike infusion (F, F(3, 45) = 2.857, ∗p = 0.0475, repeated measures ANOVA followed by Tukey’s test G, t = 2.211, ∗p = 0.0442, Student’s t test; n = 7–9 mice per group).

(H) Time spent at the center of the open field arena at early or late stages of the model (early, t = 1.728, p = 0.1021; late, t = 0.5363, p = 0.5348; Student’s t test; n = 8–10 mice per group).

(I) Total distance traveled in the open field arena at early or late stages of the model (early, t = 0.9614, p = 0.3498; late, t = 1.343, p = 0.1993; Student’s t test; n = 8–10 mice per group).

(J, K, O, and P) Representative images of the DG hippocampal region of Veh-infused (J and O) and Spike-infused mice (K and P) in the early (J and K) and late (O and P) stages of the model, immunolabeled for Homer-1 (red) and synaptophysin (SYP; green).

(L–N and Q–S) Number of puncta for Homer-1 (L and Q), SYP (M and R), and colocalized Homer-1/SYP puncta (N and S) in the early (L–N) and late (Q–S) stages of the model. (L, t = 1.202, p = 0.2524; M, t = 0.6648, p = 0.5188; N, t = 0.04952, p = 0.9613; Q, t = 0.7491, p = 0.4711; R, t = 3.400, ∗p = 0.0273; S, t = 4.204, ∗p = 0.0137; Student’s t test; n = 6–7 mice per group).

Scale bar, 20 μm. Symbols represent individual mice. Bars or points represent mean ± SEM. IHC, immunohistochemistry; MWM, Morris water maze; NOR, novel object recognition.