Skip to main content
. 2023 Feb 1;43(5):863–877. doi: 10.1523/JNEUROSCI.0984-22.2022

Figure 1.

Figure 1.

In LPS-induced inflammatory conditions, lumateperone conferred anti-inflammatory activity. The LPS dose was 500 µg/kg subcutaneously, and lumateperone or vehicle were coinjected intraperitoneally, immediately thereafter. Samples were collected 2 h after these injections, and mRNA was analyzed by qRT-PCR or NanoString Neuropath panel and serum by multiplex. A, A dose–response was performed for lumateperone at 0.3, 3, and 8 mg/kg. Results show hippocampal mRNA levels of Il1b, Tnfa, Il6, and Il10 mRNA normalized to the control group (in blue) using the Dct method; n = 5–12 per group. B, The ability of lumateperone to normalize inflammation levels was confirmed in serum. Protein levels from blood serum were analyzed by Multiplex MSD assay V-Plex technology and expressed in pg/ml for IL-1β, TNF-α, and IL-10, and in ng/ml for IL-6. C, The same study design was followed for NanoString analyses. D, Directed global significance scores were calculated by nSolver software, which measures the extent to which a given gene set is upregulated or downregulated relative to a given covariate; the control group was used as the reference in this experiment. E, Top genes involved in microglia function, neuroprotection, and inflammation that were altered (log2, p value, lower value, upper value) in LPS+Luma versus LPS groups. F, Hierarchical clustering heatmap of LPS+Luma versus LPS showing significant genes upregulated (in orange) or downregulated (in blue) in hippocampal tissue. G, Venn diagrams revealed poor overlap of significantly altered gene expression changes (p ≤ 0.04999) when group comparisons were performed. Graphs are mean ± SEM; n = 3-7 per group. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, one-way ANOVA followed by Bonferroni multiple comparison test. For NanoString analyses, see Extended Data Figure 1-1 for a list of housekeeping genes that were used for expression normalization. BDNF, brain-derived neurotrophic factor; Contr, Control; Dct, δ ct; Luma, lumateperone; RAGE, receptor for advanced glycation end products; tnfa, tumor necrosis factor-α; Veh, vehicle.