ArticlePLoS medicine2008
A mechanism for the inhibition of neural progenitor cell proliferation by cocaine.
Article in PLoS medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 70 citations in OpenAlex.
- Cocaine perturbs neurodevelopment and increases neuroinflammation in a prenatal cerebral organoid model.Translational psychiatry · 2025Article
- Reactive Oxygen Species Mediate Transcriptional Responses to Dopamine and Cocaine in Human Cerebral Organoids.International journal of molecular sciences · 2023Article
- The Effects of Environmental Adversities on Human Neocortical Neurogenesis Modeled in Brain Organoids.Frontiers in molecular biosciences · 2021Review
- The cellular basis of fetal endoplasmic reticulum stress and oxidative stress in drug-induced neurodevelopmental deficits.Neurobiology of stress · 2019Review
- Non-canonical Targets Mediating the Action of Drugs of Abuse: Cocaine at the Sigma-1 Receptor as an Example.Frontiers in neuroscience · 2019Article
- Cocaine-mediated activation of microglia and microglial MeCP2 and BDNF production.Neurobiology of disease · 2018Article
- Modeling Neurological Diseases With Human Brain Organoids.Frontiers in synaptic neuroscience · 2018Review
- 3D brain Organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders.Journal of biomedical science · 2017Review
- CYP3A5 Mediates Effects of Cocaine on Human Neocorticogenesis: Studies using an In Vitro 3D Self-Organized hPSC Model with a Single Cortex-Like Unit.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Article
- Cocaine promotes primary human astrocyte proliferation via JNK-dependent up-regulation of cyclin A2.Restorative neurology and neuroscience · 2016Article
- Cocaine-induced neurodevelopmental deficits and underlying mechanisms.Birth defects research. Part C, Embryo today : reviews · 2016Review
- Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Effects of addictive drugs on adult neural stem/progenitor cells.Cellular and molecular life sciences : CMLS · 2016Review
- Transcriptomic and genetic studies identify NFAT5 as a candidate gene for cocaine dependence.Translational psychiatry · 2015Article
- Cocaine induces nuclear export and degradation of neuronal retinoid X receptor-γ via a TNF-α/JNK- mediated mechanism.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2015Article
- An in vitro model of human neocortical development using pluripotent stem cells: cocaine-induced cytoarchitectural alterations.Disease models & mechanisms · 2014Article
- Neurobehavioral and Developmental Traiectories Associated with Level of Prenatal Cocaine Exposure.Journal of neurology and psychology · 2014Article
- Effects of prenatal cocaine/polydrug exposure on substance use by age 15.Drug and alcohol dependence · 2014Article
- Interactions of HIV and drugs of abuse: the importance of glia, neural progenitors, and host genetic factors.International review of neurobiology · 2014Review
- Comparison of 12-year-old children with prenatal exposure to cocaine and non-exposed controls on caregiver ratings of executive function.Journal of youth and adolescence · 2014Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundPrenatal exposure of the developing brain to cocaine causes morphological and behavioral abnormalities. Recent studies indicate that cocaine-induced proliferation inhibition and/or apoptosis in neural progenitor cells may play a pivotal role in causing these abnormalities. To understand the molecular mechanism through which cocaine inhibits cell proliferation in neural progenitors, we sought to identify the molecules that are responsible for mediating the effect of cocaine on cell cycle regulation. METHODS AND
findingsMicroarray analysis followed by quantitative real-time reverse transcription PCR was used to screen cocaine-responsive and cell cycle-related genes in a neural progenitor cell line where cocaine exposure caused a robust anti-proliferative effect by interfering with the G1-to-S transition. Cyclin A2, among genes related to the G1-to-S cell cycle transition, was most strongly down-regulated by cocaine. Down-regulation of cyclin A was also found in cocaine-treated human primary neural and A2B5+ progenitor cells, as well as in rat fetal brains exposed to cocaine in utero. Reversing cyclin A down-regulation by gene transfer counteracted the proliferation inhibition caused by cocaine. Further, we found that cocaine-induced accumulation of reactive oxygen species, which involves N-oxidation of cocaine via cytochrome P450, promotes cyclin A down-regulation by causing an endoplasmic reticulum (ER) stress response, as indicated by increased phosphorylation of eIF2alpha and expression of ATF4. In the developing rat brain, the P450 inhibitor cimetidine counteracted cocaine-induced inhibition of neural progenitor cell proliferation as well as down-regulation of cyclin A.
conclusionsOur results demonstrate that down-regulation of cyclin A underlies cocaine-induced proliferation inhibition in neural progenitors. The down-regulation of cyclin A is initiated by N-oxidative metabolism of cocaine and consequent ER stress. Inhibition of cocaine N-oxidative metabolism by P450 inhibitors may provide a preventive strategy for counteracting the adverse effects of cocaine on fetal brain development.
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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.