Developmental neurotoxicants target neurodifferentiation into the serotonin phenotype: Chlorpyrifos, diazinon, dieldrin and divalent nickel

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Oxidative and Excitatory Mechanisms of Developmental Neurotoxicity: Transcriptional Profiles for Chlorpyrifos, Diazinon, Dieldrin, and Divalent Nickel in PC12 Cells

BACKGROUND Oxidative stress and excitotoxicity underlie the developmental neurotoxicity of numerous chemicals. OBJECTIVES We compared the effects of organophosphates (chlorpyrifos and diazinon), an organo-chlorine (dieldrin), and a metal [divalent nickel (Ni2+)] to determine how these mechanisms contribute to similar or dissimilar neurotoxic outcomes. METHODS We used PC12 cells as a model o...

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Transcriptional profiles for glutamate transporters reveal differences between organophosphates but similarities with unrelated neurotoxicants.

The developmental neurotoxicity of organophosphates involves mechanisms other than their shared property as cholinesterase inhibitors, among which are excitotoxicity and oxidative stress. We used PC12 cells as a neurodevelopmental model to compare the effects of chlorpyrifos and diazinon on the expression of genes encoding glutamate transporters. Chlorpyrifos had a greater effect in cells under...

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Screening for Developmental Neurotoxicity Using PC12 Cells: Comparisons of Organophosphates with a Carbamate, an Organochlorine, and Divalent Nickel

BACKGROUND In light of the large number of chemicals that are potential developmental neurotoxicants, there is a need to develop rapid screening techniques. OBJECTIVES We exposed undifferentiated and differentiating neuronotypic PC12 cells to different organophosphates (chlorpyrifos, diazinon, parathion), a carbamate (physostigmine), an organochlorine (dieldrin), and a metal (divalent nickel;...

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Nonenzymatic Functions of Acetylcholinesterase Splice Variants in the Developmental Neurotoxicity of Organophosphates: Chlorpyrifos, Chlorpyrifos Oxon, and Diazinon

BACKGROUND Organophosphate pesticides affect mammalian brain development through mechanisms separable from the inhibition of acetylcholinesterase (AChE) enzymatic activity and resultant cholinergic hyperstimulation. In the brain, AChE has two catalytically similar splice variants with distinct functions in development and repair. The rare, read-through isoform, AChE-R, is preferentially induced...

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Adverse Benzo[a]pyrene Effects on Neurodifferentiation Are Altered by Other Neurotoxicant Coexposures: Interactions with Dexamethasone, Chlorpyrifos, or Nicotine in PC12 Cells

BACKGROUND Polycyclic aromatic hydrocarbons are suspected developmental neurotoxicants, but human exposures typically occur in combination with other neurotoxic contaminants. OBJECTIVE AND METHODS We explored the effects of benzo[a]pyrene (BaP) on neurodifferentiation in PC12 cells, in combination with a glucocorticoid (dexamethasone, used in preterm labor), an organophosphate pesticide (chlo...

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ژورنال

عنوان ژورنال: Toxicology and Applied Pharmacology

سال: 2008

ISSN: 0041-008X

DOI: 10.1016/j.taap.2008.08.020