Present and Future Modeling of Human Psychiatric Connectopathies With Brain Organoids.

Autor: Urenda JP; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Del Dosso A; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Birtele M; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California., Quadrato G; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: giorgia.quadrato@med.usc.edu.
Jazyk: angličtina
Zdroj: Biological psychiatry [Biol Psychiatry] 2023 Apr 01; Vol. 93 (7), pp. 606-615. Date of Electronic Publication: 2022 Dec 23.
DOI: 10.1016/j.biopsych.2022.12.017
Abstrakt: 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.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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