The molecular footprint of valproic acid in human hippocampal organoid.

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental condition characterized by neuroinflammation, and disruption in neuronal development. Valproic acid (VPA) is a known environmental risk factor for ASD. Induced pluripotent stem cells (IPSCs IMR90-4)-derived human hippocampal organoids (hHOs) at 60 days of development were used to investigate VPA-induced changes in mRNA and microRNA (miRNA) profiles. The molecular effects of VPA on hHOs were deciphered by meaningfully integrating the ability of miRNA to regulate expression of their predicted mRNA targets crucial to altering neuroinflammatory pathways. Molecular footprint can be defined as the VPA-induced changes to the miRNA profile resulting in coordinated post-transcriptional (mRNA) regulation of neuronal and inflammatory pathways associated with ASD. Based on the results, the molecular footprint of VPA in hHOs was generated for the first time. These findings highlight the contribution of miRNA-mediated regulatory mRNA networks to VPA-induced neuroinflammation-associated with ASD in hHOs.