Excitatory dysfunction drives network and calcium handling deficits in 16p11.2 duplication schizophrenia iPSC-derived neurons

Authors: Parnell E, Culotta L, Forrest MP, Jalloul HA, Eckman BL, Loizzo DD, Horan KKE, Dos Santos M, Piguel NH, Tai DJC, Zhang H, Gertler TS, Simkin D, Sanders AR, Talkowski ME, Gejman PV, Kiskinis E, Duan J, Penzes P

Biological Psychiatry, 2022

 

 

Researchers use Axion’s Maestro MEA to understand the role of 16p11.2 duplication in early neurodevelopment and schizophrenia pathophysiology.

Research has demonstrated that neuronal deficits are associated with schizophrenia—a mental health disorder sometimes linked to copy number variants at chromosome 16p11.2—but the effects of 16p11.2 duplication on early neurodevelopment are not well understood. In this study, scientists use human induced pluripotent stem cell (hiPSC)-derived neurons on Axion’s noninvasive Maestro multielectrode array (MEA) platform, and other methods, to examine the contribution of 16p11.2 duplication on the pathogenesis of schizophrenia. The MEA studies showed that patient-derived 16p11.2 duplication neurons displayed reduced firing and synchrony at later stages of in vitro maturation, supporting the overall findings that “strongly implicate deregulated calcium homeostasis, neuronal network properties, and morphological development as 16p11.2 duplication-dependent mechanisms that impair neurodevelopment and contribute to SCZ pathophysiology.”