Present and Future Modeling of Human Psychiatric Connectopathies With Brain Organoids.
Publication Year:
2023
PubMed ID:
36759258
Funding Grants:
Public Summary:
Scientists are using mini-brain structures called brain organoids, grown from human stem cells, to study neuropsychiatric disorders like autism and schizophrenia. These organoids are valuable tools for understanding how these disorders affect the development and behavior of brain cells. So far, most studies have focused on how these disorders impact the growth and function of individual brain cells in the cerebral cortex, which is the outer layer of the brain. However, these disorders involve problems with how different brain regions connect and communicate with each other. Brain organoids, in their current form, have limitations in reproducing these connections, which hinders our ability to study brain connectivity at both the cellular and larger scale. In this perspective, the authors discuss the current use of brain organoids to model neuropsychiatric disorders, highlighting their potential and limitations in representing functional connectivity between different brain regions. They also emphasize the need for interdisciplinary approaches to develop more advanced brain organoids that can better mimic the problems in brain connections seen in psychiatric disorders. This could lead to improved models for studying and eventually treating these conditions.
Scientific Abstract:
Brain organoids derived from human pluripotent stem cells are emerging as a powerful tool to model cellular aspects of neuropsychiatric disorders, including alterations in cell proliferation, differentiation, migration, and lineage trajectory. To date, most contributions in the field have focused on modeling cellular impairment of the cerebral cortex, with few studies probing dysfunction in local network connectivity. However, it is increasingly more apparent that these psychiatric disorders are connectopathies involving multiple brain structures and the connections between them. Therefore, the lack of reproducible anatomical features in these 3-dimensional cultures represents a major bottleneck for effectively modeling brain connectivity at the micro(cellular) level and at the macroscale level between brain regions. In this perspective, we review the use of current organoid protocols to model neuropsychiatric disorders with a specific emphasis on the potential and limitations of the current strategies to model impairments in functional connectivity. Finally, we discuss the importance of adopting interdisciplinary strategies to establish next-generation, multiregional organoids that can model, with higher fidelity, the dysfunction in the development and functionality of long-range connections within the brain of patients affected by psychiatric disorders.