Topic: 16p11.2 deletion

Noradrenaline (NA) is a strong modulator of neuronal activity and many autism spectrum disorder (ASD) symptoms can be attributed to maladaptive activity of locus coeruleus (LC), the main source of forebrain NA. Our lab recently uncovered a role for dysregulated LC-NA function in motor learning delays of the 16p11.2 deletion (+/-) mouse-model of ASD. We found that reduced NA levels in primary motor cortex (M1) caused delays in motor learning and increased neuronal activity in M1 pyramidal neurons. Both behavioral and neuronal phenotypes were rescued by chemogenetic activation of LC-NA. We next

The autism spectrum disorder (ASD)-associated 16p11.2 gene quinolinate phosphoribosyltransferase (QPRT) is essential for neuronal differentiation but not proliferation of SH-SY5Y neuroblastoma cells. QPRT is part of tryptophan metabolism and catabolizes quinolinic acid (QUIN), a NMDA-R agonist neurotoxic for glutamatergic cells. However, we can exclude a QUIN-driven neurotoxicity in the SH-SY5Y model. In primary human neural progenitor cells, chemical inhibition of QPRT using phthalic acid (PA) leads to premature differentiation and a shift from neurons to astrocytes. Here, we employed cerebra