Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Environ Health Perspect
2001 Jul 01;1097:651-61. doi: 10.1289/ehp.01109651.
Show Gene links
Show Anatomy links
An invertebrate model of the developmental neurotoxicity of insecticides: effects of chlorpyrifos and dieldrin in sea urchin embryos and larvae.
Buznikov GA
,
Nikitina LA
,
Bezuglov VV
,
Lauder JM
,
Padilla S
,
Slotkin TA
.
???displayArticle.abstract???
Chlorpyrifos targets mammalian brain development through a combination of effects directed at cholinergic receptors and intracellular signaling cascades that are involved in cell differentiation. We used sea urchin embryos as an invertebrate model system to explore the cellular mechanisms underlying the actions of chlorpyrifos and to delineate the critical period of developmental vulnerability. Sea urchin embryos and larvae were exposed to chlorpyrifos at different stages of development ranging from early cell cleavages through the prism stage. Although early cleavages were unaffected even at high chlorpyrifos concentrations, micromolar concentrations added at the mid-blastula stage evoked a prominent change in cell phenotype and overall larval structure, with appearance of pigmented cells followed by their accumulation in an extralarval cap that was extruded from the animal pole. At higher concentrations (20-40 microM), these abnormal cells constituted over 90% of the total cell number. Studies with cholinergic receptor blocking agents and protein kinase C inhibitors indicated two distinct types of effects, one mediated through stimulation of nicotinic cholinergic receptors and the other targeting intracellular signaling. The effects of chlorpyrifos were not mimicked by chlorpyrifos oxon, the active metabolite that inhibits cholinesterase, nor by nonorganophosphate cholinesterase inhibitors. Dieldrin, an organochlorine that targets GABA(A )receptors, was similarly ineffective. The effects of chlorpyrifos and its underlying cholinergic and signaling-related mechanisms parallel prior findings in mammalian embryonic central nervous system. Invertebrate test systems may thus provide both a screening procedure for potential neuroteratogenesis by organophosphate-related compounds, as well as a system with which to uncover novel mechanisms underlying developmental vulnerability.
Auman,
Neonatal chlorpyrifos exposure targets multiple proteins governing the hepatic adenylyl cyclase signaling cascade: implications for neurotoxicity.
2000, Pubmed
Auman,
Neonatal chlorpyrifos exposure targets multiple proteins governing the hepatic adenylyl cyclase signaling cascade: implications for neurotoxicity.
2000,
Pubmed
Bagchi,
In vitro and in vivo induction of heat shock (stress) protein (Hsp) gene expression by selected pesticides.
1996,
Pubmed
Bagchi,
In vitro and in vivo generation of reactive oxygen species, DNA damage and lactate dehydrogenase leakage by selected pesticides.
1995,
Pubmed
Barone,
Vulnerable processes of nervous system development: a review of markers and methods.
2000,
Pubmed
Brannen,
Prenatal exposure to neurotoxicants dieldrin or lindane alters tert-butylbicyclophosphorothionate binding to GABA(A) receptors in fetal rat brainstem.
1998,
Pubmed
Buznikov,
From oocyte to neuron: do neurotransmitters function in the same way throughout development?
1996,
Pubmed
Buznikov,
Cholinoreceptors of early (preneural) sea urchin embryos.
2000,
Pubmed
,
Echinobase
Buznikov,
The role of neurohumours in early embryogenesis. 3. Pharmacological analysis of the role of neurohumours in cleavage divisions.
1970,
Pubmed
Campbell,
Chlorpyrifos interferes with cell development in rat brain regions.
1997,
Pubmed
Cao,
Cytotoxicity of organophosphate anticholinesterases.
1999,
Pubmed
Chanda,
Neurochemical and neurobehavioral effects of repeated gestational exposure to chlorpyrifos in maternal and developing rats.
1996,
Pubmed
Chaudhuri,
Differential modulation of organophosphate-sensitive muscarinic receptors in rat brain by parathion and chlorpyrifos.
1993,
Pubmed
Cosenza,
Effects of chlorpyrifos on neuronal development in rat embryo midbrain micromass cultures.
1995,
Pubmed
Crumpton,
Developmental neurotoxicity of chlorpyrifos in vivo and in vitro: effects on nuclear transcription factors involved in cell replication and differentiation.
2000,
Pubmed
Crumpton,
Is oxidative stress involved in the developmental neurotoxicity of chlorpyrifos?
2000,
Pubmed
Dam,
Neonatal chlorpyrifos exposure alters synaptic development and neuronal activity in cholinergic and catecholaminergic pathways.
1999,
Pubmed
Dam,
Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration.
1998,
Pubmed
Dam,
Chlorpyrifos releases norepinephrine from adult and neonatal rat brain synaptosomes.
1999,
Pubmed
Dam,
Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity.
2000,
Pubmed
Das,
Neuronal differentiation in PC12 cells is inhibited by chlorpyrifos and its metabolites: is acetylcholinesterase inhibition the site of action?
1999,
Pubmed
Davis,
Exposures from indoor spraying of chlorpyrifos pose greater health risks to children than currently estimated.
1998,
Pubmed
Ehrich,
Acetylcholinesterase and neuropathy target esterase inhibitions in neuroblastoma cells to distinguish organophosphorus compounds causing acute and delayed neurotoxicity.
1997,
Pubmed
Falugi,
Localization and possible role of molecules associated with the cholinergic system during "non-nervous" developmental events.
1993,
Pubmed
Fenske,
Potential exposure and health risks of infants following indoor residential pesticide applications.
1990,
Pubmed
Gurunathan,
Accumulation of chlorpyrifos on residential surfaces and toys accessible to children.
1998,
Pubmed
Gustafson,
On the role of serotonin and acetylcholine in sea urchin morphogenesis.
1970,
Pubmed
,
Echinobase
Huff,
In vitro effect of chlorpyrifos oxon on muscarinic receptors and adenylate cyclase.
1995,
Pubmed
Huff,
Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum.
1994,
Pubmed
Hunter,
Gestational exposure to chlorpyrifos: comparative distribution of trichloropyridinol in the fetus and dam.
1999,
Pubmed
Ivonnet,
Nicotinic acetylcholine receptors of the neuronal type occur in the plasma membrane of sea urchin eggs.
1997,
Pubmed
,
Echinobase
Katz,
Chlorpyrifos, parathion, and their oxons bind to and desensitize a nicotinic acetylcholine receptor: relevance to their toxicities.
1997,
Pubmed
Landrigan,
Pesticides and inner-city children: exposures, risks, and prevention.
1999,
Pubmed
Li,
Organophosphorus neuropathy target esterase inhibitors selectively block outgrowth of neurite-like and cell processes in cultured cells.
1998,
Pubmed
Liu,
Effects of chlorpyrifos on high-affinity choline uptake and [3H]hemicholinium-3 binding in rat brain.
1996,
Pubmed
Liu,
Comparative presynaptic neurochemical changes in rat striatum following exposure to chlorpyrifos or parathion.
1998,
Pubmed
Liu,
Prenatal exposure to the pesticide dieldrin or the GABA(A) receptor antagonist bicuculline differentially alters expression of GABA(A) receptor subunit mRNAs in fetal rat brainstem.
1998,
Pubmed
May,
Disturbing behavior: neurotoxic effects in children.
2000,
Pubmed
Monnet-Tschudi,
Maturation-dependent effects of chlorpyrifos and parathion and their oxygen analogs on acetylcholinesterase and neuronal and glial markers in aggregating brain cell cultures.
2000,
Pubmed
Morale,
Biological effects of a neurotoxic pesticide at low concentrations on sea urchin early development. A terathogenic assay.
1998,
Pubmed
,
Echinobase
Nagata,
Direct actions of anticholinesterases on the neuronal nicotinic acetylcholine receptor channels.
1997,
Pubmed
Narahashi,
Ion channels as targets for insecticides.
1998,
Pubmed
Padilla,
Comparison of the role of esterases in the differential age-related sensitivity to chlorpyrifos and methamidophos.
2000,
Pubmed
Pope,
Organophosphorus pesticides: do they all have the same mechanism of toxicity?
1999,
Pubmed
Roy,
Chlorpyrifos elicits mitotic abnormalities and apoptosis in neuroepithelium of cultured rat embryos.
1998,
Pubmed
Roy,
Nicotine evokes cell death in embryonic rat brain during neurulation.
1998,
Pubmed
Shmukier,
Functional coupling of neurotransmitters with second messengers during cleavage divisions: facts and hypotheses.
1998,
Pubmed
Slotkin,
Development of [3H]nicotine binding sites in brain regions of rats exposed to nicotine prenatally via maternal injections or infusions.
1987,
Pubmed
Slotkin,
Developmental cholinotoxicants: nicotine and chlorpyrifos.
1999,
Pubmed
Song,
Cellular mechanisms for developmental toxicity of chlorpyrifos: targeting the adenylyl cyclase signaling cascade.
1997,
Pubmed
Song,
Modeling the developmental neurotoxicity of chlorpyrifos in vitro: macromolecule synthesis in PC12 cells.
1998,
Pubmed
Steingart,
Pre- and postsynaptic alterations in the septohippocampal cholinergic innervations after prenatal exposure to drugs.
1998,
Pubmed
Steingart,
Neural grafting reverses prenatal drug-induced alterations in hippocampal PKC and related behavioral deficits.
2000,
Pubmed
Ward,
Organophosphorus compounds preferentially affect second messenger systems coupled to M2/M4 receptors in rat frontal cortex.
1996,
Pubmed
Whitney,
Developmental neurotoxicity of chlorpyrifos: cellular mechanisms.
1995,
Pubmed
