Figure 1.

Administration of SARS-CoV-2 S1 protein induces cognitive deficit and anxiety-like behavior in mice. (a) Experimental design of S1 administration and behavioral tests. S1 protein (n = 10) or saline (Control, n = 10) was administered to C57BL/6 mice at 8 weeks of age, and behavioral tests were started 1 week after the administration. (b) Cognitive deficits were assessed using novel object recognition (NOR, left) or novel location recognition (NLR, right) tests and are presented as discrimination index percentages. Locomotor activity was measured by the total distance moved by mice in the chamber within a test session (bottom). The exploration time of a novel object or location divided by total exploration time was presented as the discrimination index of the novel object or location. The pink circle indicates a novel object or novel location. Anxiety-like behavior was assessed using the elevated plus maze test (EPM, panel c) and the open field test (OFT, panel d). (c) EPM trace of Control and S1 protein-injected groups (upper); the time spent in the open arm (dotted) vs. the closed arm (solid) in the EPM (bottom). (d) The center and periphery zones in the OFT are shown (upper). The time spent in the center vs. periphery zones in the OFT was examined (bottom). All representative navigations on the behavior test for a 5-min period are presented for the mice. The data are presented as the mean ± s.e.m. Statistical results are for unpaired t-tests. IHC, immunohistochemistry. ** p < 0.01, * p < 0.05.