Human in vitro models for understanding mechanisms of autism spectrum disorder

Abstract

Early brain development is a critical epoch for the development of autism spectrum disorder (ASD). In vivo animal models have, until recently, been the principal tool used to study early brain development and the changes occurring in neurodevelopmental disorders such as ASD. In vitro models of brain development represent a significant advance in the field. Here, we review the main methods available to study human brain development in vitro and the applications of these models for studying ASD and other psychiatric disorders. We discuss the main findings from stem cell models to date focusing on cell cycle and proliferation, cell death, cell differentiation and maturation, and neuronal signaling and synaptic stimuli. To be able to generalize the results from these studies, we propose a framework of experimental design and power considerations for using in vitro models to study ASD. These include both technical issues such as reproducibility and power analysis and conceptual issues such as the brain region and cell types being modeled.Early development as a critical period for ASD susceptibility

Mind the translational gap: using iPS cell models to bridge from genetic discoveries to perturbed pathways and therapeutic targets

“…The phenotypic diversity observed in many individuals with ASD is representative of the underlying heterogeneity of their genetic background and is also reflected on the diversity of reported cellular phenotypes observed across iPSC models. Comprehensive catalogues of ASD-relevant cellular phenotypes as well as detailed description of current Biobanks of deposited patient-derived cell material, have been compiled in a number of excellent reviews [71,72]. However, it is often challenging to compare qualitative observations, and the field would certainly benefit form adapting standardized quantitative measures to evaluate the impact of genetic background on cellular phenotypes.…”

Linking Autism Risk Genes to Disruption of Cortical Development

“…In the next sections, we will discuss the evidence in rodent models implicating high-risk ASD genes [ 6 , 7 , 8 , 38 ] in cortical development. We note that cortical alterations have also emerged in mouse [ 86 , 87 , 88 ] and stem cell models (reviewed in [ 89 ]) of CNVs associated with ASD risk. We will not discuss the circuit changes and behavioral outcomes of the rodent models with mutations in ASD risk genes, which are discussed elsewhere [ 90 , 91 , 92 ].…”

Differential Diagnosis of Landau-Kleffner Syndrome Versus Post Encephalitis Syndrome in a 13-year-old Boy With Autism Spectrum Disorder

“…While the causative reason for ASD remains unknown, it is generally believed that genetic factors play a heavy role. It is hypothesized that an abnormal gene is expressed in early fetal development [11]. This theory is supported by the high risk for ASD between siblings and the higher prevalence among males.…”