Table 1. KMO and HAAO knock-out mice brain and plasma kynurenine metabolite analysis following peripheral inflammation.
|
Genotype |
Main effects |
Interaction | |||||||
|---|---|---|---|---|---|---|---|---|---|
|
WT |
KMO−/− |
HAAO−/− |
Treatment P-value | Genotype P-value | Treatment × genotype | ||||
| Saline | LPS | Saline | LPS | Saline | LPS | ||||
| Brain metabolites (μM) | |||||||||
| Tryptophan | 31.20 (2.1) | 34.44 (2.9) | 37.54 (8.0) | 45.25 (8.0) | 55.49 (3.3) | 67.96 (0.9) | P<0.05 | P<0.001 | n.s. |
| Kynurenine | 0.17 (0.01) | 0.59 (0.06)** | 2.95 (0.2)+++ | 3.82 (0.3)***,+++ | 0.32 (0.05) | 2.02 (0.1)***,+++ | P<0.001 | P<0.001 | P<0.001 |
| 3-HK | 0.044 (0.007) | 0.17 (0.03)*** | n.d. | n.d. | 0.54 (0.2) | 0.51 (0.08) | n/a | n/a | n/a |
| 3-HAA | 0.29 (0.06) | 0.25 (0.04) | 0.26 (0.03) | 0.12 (0.04) | 0.99 (0.07)+++ | 0.44 (0.05)***,++ | P<0.001 | P<0.001 | P<0.001 |
| QA | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. | n/a | n/a | n/a |
| KA | 0.12 (0.04) | 0.10 (0.02) | 0.37 (0.08) | 0.31 (0.05) | 0.021 (0.002) | 0.038 (0.001) | n.s. | P<0.001 | n.s. |
| Plasma metabolites (μM) | |||||||||
| Tryptophan | 96.00 (4.7) | 78.36 (7.4) | 65.72 (3.9) | 49.39 (2.6) | 120.62 (9.5) | 98.23 (3.0) | P<0.05 | P<0.001 | n.s. |
| Kynurenine | 0.80 (0.06) | 2.41 (0.1) | 11.13 (2.0) | 9.86 (0.3) | 0.88 (0.08) | 3.19 (0.4) | n.s. | P<0.001 | n.s. |
| 3-HK | 0.083 (0.01) | 0.45 (0.03)*** | 0.0098 (0.002) | 0.017 (0.006)+++ | 0.13 (0.02) | 0.87 (0.08)***,+++ | P<0.001 | P<0.001 | P<0.001 |
| 3-HAA | n.d. | n.d. | n.d. | n.d. | 2.17 (0.27) | 3.16 (1.0) | n/a | n/a | n/a |
| QA | 0.39 (0.03) | 0.48 (0.08) | 0.24 (0.008) | 0.30 (0.004) | 0.64 (0.04) | 0.58 (0.02) | n.s. | P<0.001 | n.s. |
| KA | 0.94 (0.1) | 0.59 (0.07) | 31.45 (5.3)+++ | 15.78 (0.8)***,+++ | 0.24 (0.04) | 0.21 (0.02) | P<0.001 | P<0.001 | P<0.001 |
Abbreviations: HAAO, 3-hydroxyanthranilic acid dioxygenase; i.p., intraperitoneal; KA, kynurenic acid; KMO, kynurenine 3-monooxygenase; LC/MS, liquid chromatography/mass spectrometry; LPS, lipopolysaccharide; n/a, statistical analysis not applicable; n.d., metabolite concentrations not reported because of high number of samples that were not detected with the LC/MS method utilized to analyze the samples; n.s., no significant difference; QA, quinolinic acid; WT, wild type; 3-HAA, 3-hydroxyanthranilic acid; 3-HK, 3-hydroxykynurenine.
Kynurenine metabolites (tryptophan, kynurenine, KA, 3-HK, 3-HAA and QA) were quantified (μM) by LC/MS in the plasma and whole-brain samples from WT, KMO−/− and HAAO−/− mice following i.p. treatment with saline or LPS (0.5 mg kg−1). Concentration values represent sample mean (s.e.m.). n=4–15 samples per group.
*Main effect or post hoc comparison between saline and LPS within the same genotype.
+Post hoc comparison with WT with the same i.p. treatment
.
*,+P<0.05–0.01; **,++P<0.01–0.001; ***,+++P<0.001.