Study on cellular pathology and functions in induced pluripotent stem cell (iPSC)-derived neurons from an autism spectrum disorder (ASD) patient

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder which is characterized by difficulties in social communication, social interaction, repetitive and restricted behaviors. Most research on ASD until now has been based on mouse genetic models. However, due to the heterogeneity of ASD and the inadequacy of the mouse model system, there were many cases that drugs verified in mouse model fail in clinical stage. In addition, ASD pathology was largely unknown. Recent technical advances in induced pluripotent stem cell (iPSC) fields enabled us to perform research on human cellular model system. In this study, we generated human neurons from ASD patient-derived iPSCs and investigated cellular phenotypes compared to human neurons from healthy people-derived iPSCs. Surprisingly, we found that NMDA currents were significantly reduced in ASD neurons by performing whole-cell patch clamp recording. In addition, the mRNA expressions of NMDAR subunits and CaMKII which is NMDAR downstream signaling molecule were significantly decreased in ASD neurons. Our finding suggests a possibility that ASD neurons are disrupted in NMDAR related signaling.