George C Gabriel, Hisato Yagi, Tuantuan Tan, Abha S Bais, Benjamin J Glennon, Margaret C Stapleton, Lihua Huang, William T Reynolds, Marla G Shaffer, Madhavi Ganapathiraju, Dennis Simon, Ashok Panigrahy, Yijen L Wu, Cecilia W Lo
Poor neurodevelopment is often observed with congenital heart disease (CHD), especially with mutations in chromatin modifiers. Here analysis of mice with hypoplastic left heart syndrome (HLHS) arising from mutations in Sin3A associated chromatin modifier Sap130 , and adhesion protein Pcdha9, revealed neurodevelopmental and neurobehavioral deficits reminiscent of those in HLHS patients. Microcephaly was associated with impaired cortical neurogenesis, mitotic block, and increased apoptosis. Transcriptional profiling indicated dysregulated neurogenesis by REST, altered CREB signaling regulating memory and synaptic plasticity, and impaired neurovascular coupling modulating cerebral blood flow...
February 26, 2024: bioRxiv