Research Paper Volume 13, Issue 5 pp 6634—6661

CRISPR/Cas9-mediated CysLT1R deletion reverses synaptic failure, amyloidosis and cognitive impairment in APP/PS1 mice

Kynurenine pathway is involved in CysLT1R-mediated synaptic dysfunction. (A) Representative immunoblots of IDO and KYNU protein in mice hippocampus. Quantifications of (B) IDO and (C) KYNU protein levels were expressed as the ratio (in %) of the WT mice. (D) Hippocampal KYNU activities were assessed by HPLC. (E) QUIN content in the hippocampus was detected by LC-MS/MS. The colocalization of QUIN with (F) NR2A or (I) NR2B was measured by immunofluorescence, respectively. (G) The immunofluorescent signal intensity of QUIN, NR2A, and DAPI in the DG. (J) The immunofluorescent signal intensity of QUIN, NR2B, and DAPI in the DG. Quantifications of colocalization of QUIN with (H) NR2A or (K) NR2B in hippocampal DG of brain sections were analyzed. All values are mean expressed as mean ± SEM, n = 4, #P, ##P, ###P

Figure 6. Kynurenine pathway is involved in CysLT1R-mediated synaptic dysfunction. (A) Representative immunoblots of IDO and KYNU protein in mice hippocampus. Quantifications of (B) IDO and (C) KYNU protein levels were expressed as the ratio (in %) of the WT mice. (D) Hippocampal KYNU activities were assessed by HPLC. (E) QUIN content in the hippocampus was detected by LC-MS/MS. The colocalization of QUIN with (F) NR2A or (I) NR2B was measured by immunofluorescence, respectively. (G) The immunofluorescent signal intensity of QUIN, NR2A, and DAPI in the DG. (J) The immunofluorescent signal intensity of QUIN, NR2B, and DAPI in the DG. Quantifications of colocalization of QUIN with (H) NR2A or (K) NR2B in hippocampal DG of brain sections were analyzed. All values are mean expressed as mean ± SEM, n = 4, #P<0.05, ##P<0.01, ###P<0.001 vs. APP/PS1 mice.