ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Cerebral organoids as a platform to model prenatal exposure to drugs of abuse.Neural regeneration research · 2026Article
- Single rosette-based generation of uniform cortical assembloids recapitulating cellular interactions between neurons and glial cells.Nature communications · 2025Article
- Cocaine perturbs neurodevelopment and increases neuroinflammation in a prenatal cerebral organoid model.Translational psychiatry · 2025Article
- The Interface of Gene Editing with Regenerative Medicine.Engineering (Beijing, China) · 2025Article
- A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Brain organoids: A new tool for modelling of neurodevelopmental disorders.Journal of cellular and molecular medicine · 2024Review
- Multiscale engineering of brain organoids for disease modeling.Advanced drug delivery reviews · 2024Review
- Cell type specification and diversity in subpallial organoids.Frontiers in genetics · 2024Review
- Deriving early single-rosette brain organoids from human pluripotent stem cells.Stem cell reports · 2023Article
- Temporal morphogen gradient-driven neural induction shapes single expanded neuroepithelium brain organoids with enhanced cortical identity.Nature communications · 2023Article
- Reactive Oxygen Species Mediate Transcriptional Responses to Dopamine and Cocaine in Human Cerebral Organoids.International journal of molecular sciences · 2023Article
- Human pluripotent stem cell (hPSC) and organoid models of autism: opportunities and limitations.Translational psychiatry · 2023Review
- Modeling maternal cholesterol exposure reveals a reduction of neural progenitor proliferation using human cerebral organoids.Life medicine · 2023Article
- Organ Chips and Visualization of Biological Systems.Advances in experimental medicine and biology · 2023Article
- Collective behavior and self-organization in neural rosette morphogenesis.Frontiers in cell and developmental biology · 2023Review
- Merits and challenges of iPSC-derived organoids for clinical applications.Frontiers in cell and developmental biology · 2023Review
- Modeling human telencephalic development and autism-associated SHANK3 deficiency using organoids generated from single neural rosettes.Nature communications · 2022Article
- Advances in construction and modeling of functional neural circuits in vitro.Neurochemical research · 2022Article
- Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids.Cell death & disease · 2022Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Because of unavoidable confounding variables in the direct study of human subjects, it has been difficult to unravel the effects of prenatal cocaine exposure on the human fetal brain, as well as the cellular and biochemical mechanisms involved. Here, we propose a novel approach using a human pluripotent stem cell (hPSC)-based 3D neocortical organoid model. This model retains essential features of human neocortical development by encompassing a single self-organized neocortical structure, without including an animal-derived gelatinous matrix. We reported previously that prenatal cocaine exposure to rats during the most active period of neural progenitor proliferation induces cytoarchitectural changes in the embryonic neocortex. We also identified a role of CYP450 and consequent oxidative ER stress signaling in these effects. However, because of differences between humans and rodents in neocorticogenesis and brain CYP metabolism, translation of the research findings from the rodent model to human brain development is uncertain. Using hPSC 3D neocortical organoids, we demonstrate that the effects of cocaine are mediated through CYP3A5-induced generation of reactive oxygen species, inhibition of neocortical progenitor cell proliferation, induction of premature neuronal differentiation, and interruption of neural tissue development. Furthermore, knockdown of CYP3A5 reversed these cocaine-induced pathological phenotypes, suggesting CYP3A5 as a therapeutic target to mitigate the deleterious neurodevelopmental effects of prenatal cocaine exposure in humans. Moreover, 3D organoid methodology provides an innovative platform for identifying adverse effects of abused psychostimulants and pharmaceutical agents, and can be adapted for use in neurodevelopmental disorders with genetic etiologies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.