ArticleToxicological sciences : an official journal of the Society of Toxicology2014
PCB 136 atropselectively alters morphometric and functional parameters of neuronal connectivity in cultured rat hippocampal neurons via ryanodine receptor-dependent mechanisms.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 72 citations in OpenAlex.
- Article
- A primary rat neuron-astrocyte-microglia tri-culture model for studying mechanisms of neurotoxicity.Frontiers in toxicology · 2024Article
- Enantiomeric Fractions Reveal Differences in the Atropselective Disposition of 2,2',3,5',6-Pentachlorobiphenyl (PCB 95) in Wildtype,Chemical research in toxicology · 2023Article
- Oxidized linoleic acid metabolites regulate neuronal morphogenesis in vitro.Neurochemistry international · 2023Article
- Gene×environment interactions in autism spectrum disorders.Current topics in developmental biology · 2023Review
- Probing the Role of CYP2 Enzymes in the Atropselective Metabolism of Polychlorinated Biphenyls Using Liver Microsomes from Transgenic Mouse Models.Chemical research in toxicology · 2022Article
- Placenta and fetal brain share a neurodevelopmental disorder DNA methylation profile in a mouse model of prenatal PCB exposure.Cell reports · 2022Article
- Article
- Perspective on prenatal polychlorinated biphenyl exposure and the development of the progeny nervous system (Review).International journal of molecular medicine · 2021Review
- Persistent organic pollutants at the synapse: Shared phenotypes and converging mechanisms of developmental neurotoxicity.Developmental neurobiology · 2021Review
- Non-dioxin-like polychlorinated biphenyl neurotoxic equivalents found in environmental and human samples.Regulatory toxicology and pharmacology : RTP · 2021Article
- Sex and Genotype Modulate the Dendritic Effects of Developmental Exposure to a Human-Relevant Polychlorinated Biphenyls Mixture in the Juvenile Mouse.Frontiers in neuroscience · 2021Article
- Developmental Exposure to a Human-Relevant Polychlorinated Biphenyl Mixture Causes Behavioral Phenotypes That Vary by Sex and Genotype in Juvenile Mice Expressing Human Mutations That Modulate Neuronal Calcium.Frontiers in neuroscience · 2021Article
- Integrating biokinetics and in vitro studies to evaluate developmental neurotoxicity induced by chlorpyrifos in human iPSC-derived neural stem cells undergoing differentiation towards neuronal and glial cells.Reproductive toxicology (Elmsford, N.Y.) · 2020Article
- Atropselective Partitioning of Polychlorinated Biphenyls in a HepG2 Cell Culture System: Experimental and Modeling Results.Environmental science & technology · 2020Article
- Review
- Atropselective Disposition of 2,2',3,4',6-Pentachlorobiphenyl (PCB 91) and Identification of Its Metabolites in Mice with Liver-Specific Deletion of Cytochrome P450 Reductase.Chemical research in toxicology · 2020Article
- The developmental neurotoxicity of legacy vs. contemporary polychlorinated biphenyls (PCBs): similarities and differences.Environmental science and pollution research international · 2020Review
- Evidence Implicating Non-Dioxin-Like Congeners as the Key Mediators of Polychlorinated Biphenyl (PCB) Developmental Neurotoxicity.International journal of molecular sciences · 2020Review
- Linoleic acid-derived metabolites constitute the majority of oxylipins in the rat pup brain and stimulate axonal growth in primary rat cortical neuron-glia co-cultures in a sex-dependent manner.Journal of neurochemistry · 2020Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca²⁺-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (-)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (-)-PCB 136 is observed at concentrations ranging from 0.1 to 100 nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca²⁺-sensitive dye demonstrates that (-)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca²⁺ oscillations. Similarly, (-)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure.
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Registered trials
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