ArticleToxicological sciences : an official journal of the Society of Toxicology2013
A hydroxylated metabolite of flame-retardant PBDE-47 decreases the survival, proliferation, and neuronal differentiation of primary cultured adult neural stem cells and interferes with signaling of ERK5 MAP kinase and neurotrophin 3.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 49 citations in OpenAlex.
- Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.EFSA journal. European Food Safety Authority · 2024Article
- Neurodevelopmental toxicity assessment of flame retardants using a human DNT in vitro testing battery.Cell biology and toxicology · 2022Article
- Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes.The Journal of biological chemistry · 2020Article
- Hepatic Transcriptomic Patterns in the Neonatal Rat After Pentabromodiphenyl Ether Exposure.Toxicologic pathology · 2020Article
- Gut microbiome: An intermediary to neurotoxicity.Neurotoxicology · 2019Review
- Cadmium Exposure Impairs Adult Hippocampal Neurogenesis.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Carcinogenic activity of pentabrominated diphenyl ether mixture (DE-71) in rats and mice.Toxicology reports · 2018Article
- Persistent 6-OH-BDE-47 exposure impairs functional neuronal maturation and alters expression of neurodevelopmentally-relevant chromatin remodelers.Environmental epigenetics · 2018Article
- Cadmium impairs the survival and proliferation of cultured adult subventricular neural stem cells through activation of the JNK and p38 MAP kinases.Toxicology · 2017Article
- BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action.Scientific reports · 2017Article
- Extracellular Signal-Regulated Kinase 5 is Required for Low-Concentration HBioMed research international · 2017Article
- Human Excretion of Polybrominated Diphenyl Ether Flame Retardants: Blood, Urine, and Sweat Study.BioMed research international · 2017Article
- The Effects of Different Factors on the Behavior of Neural Stem Cells.Stem cells international · 2017Review
- Stem Cells in Neurotoxicology/Developmental Neurotoxicology: Current Scenario and Future Prospects.Molecular neurobiology · 2016Review
- Developmental toxicity of the PBDE metabolite 6-OH-BDE-47 in zebrafish and the potential role of thyroid receptor β.Aquatic toxicology (Amsterdam, Netherlands) · 2015Article
- Importance of being Nernst: Synaptic activity and functional relevance in stem cell-derived neurons.World journal of stem cells · 2015Review
- Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Computer-aided targeting of the PI3K/Akt/mTOR pathway: toxicity reduction and therapeutic opportunities.International journal of molecular sciences · 2014Review
- A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity.Toxicology letters · 2014Review
- The PBDE metabolite 6-OH-BDE 47 affects melanin pigmentation and THRβ MRNA expression in the eye of zebrafish embryos.Endocrine disruptors (Austin, Tex.)Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Polybrominated diphenyl ethers (PBDEs) are a group of organobromine compounds widely used as flame retardants. PBDE-47 is one of the most prominent PBDE congeners found in human tissues, and it can be transformed into several metabolites, including 6-OH-PBDE-47. Recent studies have shown that PBDE-47 is neurotoxic to animals and possibly humans. However, the basis for the neurotoxicity of PBDEs and their metabolites is unclear. For example, it is not known whether PBDEs affect adult neurogenesis, a process implicated in learning and memory and in olfactory behavior. In this study, we examined the toxicity of PBDEs for primary adult neural stem/progenitor cells (aNSCs) isolated from the subventricular zone (SVZ) of adult mice. We discovered that 6-OH-PBDE-47, but not its parent compound PBDE-47, is cytotoxic for aNCSs using MTS metabolism and cell number as a measure of cytotoxicity. Interestingly, 6-OH-PBDE-47 induced apoptosis at concentrations above 7.5μM inhibited proliferation at 2.5-5μM while suppressing neuronal and oligodendrocyte differentiation at submicromolar concentrations (≤ 1μM). The effect on proliferation was reversed upon removal of 6-OH-PBDE-47 and correlated with selective but reversible inhibition of ERK5 activation by mitogenic growth factors EGF and bFGF. 6-OH-PBDE-47 also inhibited the proneuronal differentiation effect of neurotrophin 3 (NT3) and NT3 activation of ERK5. Together, these data show that 6-OH-PBDE-47 is more toxic than its parent compound for SVZ-derived aNSCs and that it inhibits multiple aspects of adult neurogenesis. Furthermore, inhibition of ERK5 signaling may underlie the adverse effect of 6-OH-PBDE-47 on proliferation and neuronal differentiation. Our data suggest that exposure to PBDE-based flame retardants could cause neurotoxicity in the adult brain by interfering with adult neurogenesis.
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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.