Fig. 3

The KP profile is associated with decreased neuroprotection and increased neurotoxicity in EAE (experimental autoimmune encephalomyelitis) disease severity. a Schematic illustration of kynurenine pathway (KP). b and c The bar diagrams depict picolinic acid (PIC) and quinolinic acid (QUIN) ratio (PIC/QUIN) (mean ± SD) measured in the plasma (b), brain (white), and spinal cord (gray) in healthy (n = 8) and EAE cohorts (n = 6 per cohort; EAE score of cohort I, 0.5–1; II, 1.5–2; III, 3–4). d The histogram depicts ACMSD gene expression in the brain and spinal cord of healthy (clear) and EAE-induced (filled) mice. e–h The graphs represent relationship of PIC (e and f) and QUIN (g and h) between the plasma vs CNS tissues (brain (e and g) or spinal cord (f and h)). i–l The immunohistochemical staining of lumbar spinal cord of cohort III EAE mice sections showed expression of quinolinic acid (QUIN) with neuron (NeuN) (i), QUIN with astrocytes (GFAP) (j), QUIN with oligodendrocytes (k), and QUIN with monocyte lineage cells (l). Arrows show QUIN staining (brown), and arrow heads show neuronal and glial markers staining (red). Counterstain, methyl green. Scale bars 10 um; 5 um (inset). m The bar diagram depicts QPRT gene expression in the brain and spinal cord of healthy (clear) and EAE-induced (filled) mice. n The immunohistochemical staining of lumbar spinal cord of cohort III EAE mice sections showed expression of QPRT protein (n = 2). Scale × 100 and × 20 (inset). o–q The bar diagrams represent serum NAD+ (nicotinamide adenine dinucleotide (oxidized)) (o), NADH (nicotinamide adenine dinucleotide (reduced)) (p), and NAD+:NADH ratio (q) in healthy and EAE mice (mean ± SD). ***p ≤ 0.001; **p ≤ 0.01; *p ≤ 0.05. IDO-1, indoleamine 2,3- dioxygenase; KAT, kynurenine amino transferase; KMO, kynurenine monooxygenase; KYNU, kynureninase; 3HAO, 3-hydroxyanthranilate 3,4-dioxygenase; ACMSD, 2-amino-3- carboxymuconate-semialdehyde decarboxylase; QPRT, quinolinate phosphoribosyl transferase