Kynurenic acid signaling is through Ahr2 in adult zebrafish brain. (A) Catabolic cascade from tryptophan to kynurenic acid. (B) Cerebroventricular microinjection paradigm. (C,D) Immunohistochemical staining for Kat2 in control (C) and Aβ42-injected (D) adult zebrafish brain sections. (E–G) Immunohistochemical staining for S100 and PCNA in control (E), KYNA-injected (F) and L-Kynurenine-injected (G) zebrafish brain sections. (H) Quantification of proliferating glial cells of conditions in (E–G). (I) Deep sequencing reads of KYNA receptors ahr2 and gpr35 as well as other receptors of neural stem cells, il4r and ngfra. Reads for gfap is for comparison. (J) tSNE plots from single cell sequencing in adult zebrafish telencephalon in progenitor cells. Expression of gfap, ahr2 and gpr35 shown. ahr2 is the only receptor for KYNA in progenitor cells. (K) Ahr2 signaling regulates cyp1b1 expression. Cyp1b1 is present in progenitor cells as determined in single cell sequencing, and in situ hybridization. Scale bars equal 50 μm. Statistical calculations and values are provided in Table S1.
|
