Investigation of the role of microglia derived from iPSC in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with high functional impairment, where the patients present behavioral changes such as repetitive and stereotyped movements, communication deficits and socialization problems. The worldwide prevalence of ASD is very high, with about 1-2% of the world population. The diagnosis of ASD patients usually occurs at three years of age, being more common in boys. Studying the biology of autism is a challenge because of the lack of access to the cells of the nervous system of patients. In 2007, Takahashi & Yamanaka described a technology capable of generating pluripotent stem cells (called Induced Pluripotent Stem Cells, iPSC) from human somatic cells. Our group has been performing modeling of idiopathic autism in vitro through iPSC and its subsequent differentiation into CNS cells. Our results revealed that the iPSC-derived neurons of individuals with autism had changes in synaptogenesis and connectivity. In addition, our group first investigated idiopathic autistic astrocytes, the most abundant glial cells in the brain. In co-culture experiments of neurons derived from individuals with autism on healthy astrocytes, we observed that astrocytes are capable of rescuing the phenotype of autistic neurons and that astrocytes of autistic individuals have a neuroinflammatory profile. Considering also this neuroinflammatory profile, it would be fundamental to investigate in idiopathic autistic patients how another important glial cell, the microglia, behaves, since they are responsible for the immunological control of the Central Nervous System (CNS) and have never been investigated in patients with ASD. In addition, microglia have a role in synaptic plasticity, control neurogenesis, play a role in CNS maintenance and immunological activity. This project aims to investigate the cellular and molecular phenotypes of microglia of individuals with idiopathic autism. (AU)