Modeling Inflammation on Neurodevelopmental Disorders Using Pluripotent Stem Cells

Abstract

Neurodevelopmental disorders (ND) are characterized by an impairment of the nervous system during its development, with a wide variety of phenotypes based on genetic or environmental cues. There are currently several disorders grouped under ND including intellectual disabilities (ID), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorders (ASD). Although NDs can have multiple culprits with varied diagnostics, several NDs present an inflammatory component. Taking advantage of induced pluripotent stem cells (iPSC), several disorders were modeled in a dish complementing in vivo data from rodent models or clinical data. Monogenic syndromes displaying ND are more feasible to be modeled using iPSCs also due to the ability to recruit patients and clinical data available. Some of these genetic disorders are Fragile X Syndrome (FXS), Rett Syndrome (RTT), and Down Syndrome (DS). Environmental NDs can be caused by maternal immune activation (MIA), such as the infection with Zika virus during pregnancy known to cause neural damage to the fetus. Our goal in this chapter is to review the advances of using stem cell research in NDs, focusing on the role of neuroinflammation on ASD and environmental NDs studies.