Targeting notch signaling to restore neural development and behavior in mouse models of ASD - PubMed
4 hours ago
- #Notch signaling
- #Autism spectrum disorder
- #GABAergic interneurons
- Notch signaling dysregulation is identified as a shared mechanism in both hereditary and non-hereditary autism spectrum disorder (ASD) mouse models.
- Disruption occurs during embryonic forebrain development due to aberrant histone deacetylase 3-mediated epigenetic regulation, affecting vasoactive intestinal peptide-positive GABAergic interneuron (VIP-IN) specification.
- CGE-specific ablation of Notch1/2 genes in ASD models restores VIP-IN loss, normalizes excitatory-inhibitory balance, and improves social behaviors.
- A single antenatal dose of a γ-secretase inhibitor ameliorates multiple ASD-associated neuronal, behavioral, and transcriptomic changes in adult models.
- The study establishes Notch signaling as a promising therapeutic target for developmental and behavioral deficits in ASD.