ADCY1-mediated cAMP signaling pathway mediates the neuropsychiatric effects of montelukast

Human forebrain organoids (day 100) derived from U2F iPS cell line were exposed with or without 20 ng/ml and 400 ng/ml montelukast (MTK) for 7 days. Organoids were then randomly selected for RNA sequencing (RNA-seq). By performing RNA-seq analysis, we showed that MTK exposure in hFOs downregulated expression of genes enriched with multiple neuronal functions including the glutamatergic synapse. These downregulated genes were also significantly overlapped with genes reported to be associated with schizophrenia, bipolar disorder, and autism. Overall design: We generated human forebrain organoids (hFOs) from U2F iPS cell lines. On day 100 of organoid culture, hFOs derived from U2F were exposed with or without for 20 ng/ml and 400 ng/ml MTK 7 days. Three organoids in each group were randomly pooled together as one mixed sample. Five mixed samples in each group were then used for RNA-seq (BGI DNBseq, paired-end 150 bp) to identify genes affected by MTK exposure. DEGs (adjusted P value < 0.05) that identified in hFOs derived from U2F were used for Gene Ontology and KEGG pathway analysis.