Research models of neurodevelopmental disorders: The right model in the right place

Abstract

Neurodevelopmental disorders (NDDs) are a heterogeneous group of impairments that affect the development of the central nervous system leading to abnormal brain function. NDDs affect a great percentage of the population worldwide, imposing a high societal and economic burden and thus, interest in this field has widely grown in recent years. Nevertheless, the complexity of human brain development and function as well as the limitations regarding human tissue usage make their modeling challenging. Animal models play a central role in the investigation of the implicated molecular and cellular mechanisms, however many of them display key differences regarding human phenotype and in many cases, they partially or completely fail to recapitulate them. Although in vitro two-dimensional (2D) human-specific models have been highly used to address some of these limitations, they lack crucial features such as complexity and heterogeneity. In this review, we will discuss the advantages, limitations and future applications of in vivo and in vitro models that are used today to model NDDs. Additionally, we will describe the recent development of 3-dimensional brain (3D) organoids which offer a promising approach as human-specific in vitro models to decipher these complex disorders.

Keywords: animal models; brain organoids; disease modeling; malformations of cortical development; neurodevelopmental disorders; two-dimensional (2D) human-specific cultures.