Figure 6
The xCT inhibitor SSZ improves the phenotype of PSNPI. Therapeutic effect of SSZ on PSNPI. (a) BW, (b) Y-maze, (c) WRA, and (d) RR. (a) Simultaneous treatment with SSZ and LPS (L + s-SSZ) and post-symptomatic treatment with SSZ 1 h after LPS treatment (L + p-SSZ) show a tendency to improve BW loss at 3 days after LPS treatment, but the differences are not statistically significant. F (3, 188) = 2.10, p = 0.10. (b) s-SSZ and p-SSZ improves the memory disorder in LPS-treated mice. F (3, 188) = 8.73, p < 0.0001. Post hoc; LPS vs L + s-SSZ, p < 0.005; LPS vs L + p-SSZ, p < 0.001. (c) s-SSZ and p-SSZ improves depression-like hypoactivity. F (3, 188) = 4.72, p < 0.05. Post hoc; LPS vs L + s-SSZ, p < 0.05; LPS vs L + p-SSZ, p < 0.05. (d) The effect of simultaneous treatment of SSZ with LPS and post-septic treatment with SSZ on the RR score is mild and is not statistically significant. F (3, 188) = 2.93, p < 0.05. Post hoc; sham vs LPS, p < 0.005; LPS vs L + s-SSZ, p = 0.051; LPS vs L + p-SSZ, p = 0.062. (a–d; sham; n = 11, LPS; n = 13, L + s-SSZ; n = 12, L + p-SSZ; n = 12) (e) Comparison of glutamate level in extracellular space (in vivo microdialysis) at the point of 24 h after LPS treatment. Extracellular glutamate in LPS and SSZ-treated mice was significantly lower than that in LPS-treated mice. (*p < 0.01, sham; n = 4, LPS; n = 4, L + SSZ; n = 4). (f) The release of glutamate from isolated microglia derived from LPS-treated mice brain is inhibited by 1 μM SSZ (*p < 0.01, sham; n = 8, LPS; n = 8, L + SSZ; n = 3).
