Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

Qiao, Dan; Seidler, Frederic J.; Slotkin, Theodore A.

doi:10.1016/j.taap.2004.11.003

Cited by 151 publications

(150 citation statements)

References 74 publications

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“…On the contrary, there was a significant overall increase in viability (reduced staining); values for the individual time points did not achieve significance separately because of the small sample size but the effect across the two time points was significant. Just as reported previously (Qiao et al, 2005) NGF treatment alone produced a progressive rise in nonviable cells, which likely involves the increase in oxidative stress attending the early stages of differentiation and neurite formation.…”

Section: Cell Acquisition Growth and Viability In Differentiating Csupporting

confidence: 77%

“…In contrast, NGF by itself reduced viability, a finding in keeping with the rise in oxidative stress that attends early stages of differentiation (Katoh et al, 1997;Qiao et al, 2005). One possibility, then, is that DEX reduces oxidative stress in differentiating neural cells, an effect that could contribute to apparent protective actions of this treatment toward hypoxic-ischemic brain damage (Barks et al, 1991).…”

Section: Discussionmentioning

confidence: 98%

“…Accordingly, the PC12 model is particularly appropriate to evaluate the mechanisms underlying the effects of DEX on neural cell replication and differentiation into defined phenotypes. Indeed, the medium required to maintain PC12 cell replication, differentiation, and growth entails the use of sera containing endogenous glucocorticoids (Qiao et al, 2005;Song et al, 1998;Teng and Greene, 1994), so that, as with the situation in vivo, effects of DEX are exerted over and above the requisite normal concentration required to maintain neural cell development. At the same time, as with all in vitro models, the cell cultures lack many features common to the developing brain, including the ability to evaluate neuronalglial interactions or more architectural aspects of regional development.…”

Section: Introductionmentioning

confidence: 99%

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Adverse Neurodevelopmental Effects of Dexamethasone Modeled in PC12 Cells: Identifying the Critical Stages and Concentration Thresholds for the Targeting of Cell Acquisition, Differentiation and Viability

Jameson

Seidler

Qiao

et al. 2005

Neuropsychopharmacol

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The use of dexamethasone (DEX) to prevent respiratory distress in preterm infants is suspected to produce neurobehavioral deficits. We used PC12 cells to model the effects of DEX on different stages of neuronal development, utilizing exposures from 24 h up to 11 days and concentrations from 0.01 to 10 mM, simulating subtherapeutic, therapeutic, and high-dose regimens. In undifferentiated cells, even at the lowest concentration, DEX inhibited DNA synthesis and produced a progressive deficit in the number of cells as evaluated by DNA content, whereas cell growth (evaluated by the total protein to DNA ratio) and cell viability (Trypan blue exclusion) were promoted. When cell differentiation was initiated with nerve growth factor, the simultaneous inclusion of DEX still produced a progressive deficit in cell numbers and promoted cell growth and viability while retarding the development of neuritic projections as monitored by the membrane/total protein ratio. Again, even 0.01 mM DEX was effective. We next assessed effects at mid-differentiation by introducing nerve growth factor for 4 days followed by coexposure to DEX. Although effects on cell number, growth, and neurite extension were still detectable, the outcomes were generally less notable. DEX also shifted the fate of PC12 cells away from the cholinergic phenotype and toward the adrenergic phenotype, with the maximum effect achieved at the outset of differentiation. Our results indicate that DEX directly disrupts neuronal cell replication, differentiation, and phenotype at concentrations below those required for the therapy of preterm infants, providing a mechanistic link between glucocorticoid use and neurodevelopmental sequelae.

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Section: Cell Acquisition Growth and Viability In Differentiating Csupporting

confidence: 77%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Adverse Neurodevelopmental Effects of Dexamethasone Modeled in PC12 Cells: Identifying the Critical Stages and Concentration Thresholds for the Targeting of Cell Acquisition, Differentiation and Viability

Jameson

Seidler

Qiao

et al. 2005

Neuropsychopharmacol

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“…At high doses, neuronal apoptosis and oxidative stress are wellestablished consequences of CPF exposure, both in vitro and in vivo [9,18,23,42,51,76,82,93]. Adult animals treated with systemically toxic doses of sarin show major changes in the expression of apoptosis-related genes [28].…”

Section: Cpf and Dzn Cytotoxicitymentioning

confidence: 99%

Comparative developmental neurotoxicity of organophosphates in vivo: Transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems

Slotkin

Seidler

2007

Brain Research Bulletin

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193

208

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Organophosphates affect mammalian brain development through a variety of mechanisms beyond their shared property of cholinesterase inhibition. We used microarrays to characterize similarities and differences in transcriptional responses to chlorpyrifos and diazinon, assessing defined gene groupings for the pathways known to be associated with the mechanisms and/or outcomes of chlorpyrifos-induced developmental neurotoxicity. We exposed neonatal rats to daily doses of chlorpyrifos (1 mg/kg) or diazinon (1 or 2 mg/kg) on postnatal days 1-4 and evaluated gene expression profiles in brainstem and forebrain on day 5; these doses produce little or no cholinesterase inhibition. We evaluated pathways for general neural cell development, cell signaling, cytotoxicity and neurotransmitter systems, and identified significant differences for >60% of 252 genes. Chlorpyrifos elicited major transcriptional changes in genes involved in neural cell growth, development of glia and myelin, transcriptional factors involved in neural cell differentiation, cAMP-related cell signaling, apoptosis, oxidative stress, excitotoxicity, and development of neurotransmitter synthesis, storage and receptors for acetylcholine, serotonin, norepinephrine and dopamine. Diazinon had similar effects on many of the same processes but also showed major differences from chlorpyrifos. Our results buttress the idea that different organophosphates target multiple pathways involved in neural cell development but also that they deviate in key aspects that may contribute to disparate neurodevelopmental outcomes. Equally important, these pathways are compromised at exposures that are unrelated to biologically significant cholinesterase inhibition and its associated signs of systemic toxicity. The approach used here demonstrates how planned comparisons with microarrays can be used to screen for developmental neurotoxicity.

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“…neuroprotective (Qiao et al, 2005); improves cognition (Maskos et al, 2005), increases sensibility of behavioral effects of alcohol (Bowers et al, 2005); decreases sensibility to metanphetamine (Kuribara, 1999); increases dopaminergic activity (Pidoplichko et al, 1997); act on cholinergic receptors (Kobayashi et al, 1999); inhibits MAO B (Fowler et al, 1996); psychoactive (Cassels et al, 2005 stimulant, tonic (Dr. Duke, 2010) tonic (Mendes & Carlini, 2007). antioxidant (Basile et al, 2005), psychostimulant (Otobone et al, 2007).…”

Section: -21 Elephantopus Mollismentioning

confidence: 99%

Brazilian plants with possible action on the central nervous system—A study of historical sources from the 16th to 19th century

Giorgetti

Negri

Rodrigues

2007

Journal of Ethnopharmacology

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Ethnopharmacological research when grounded on historic literature has for its objective retrieving traditional knowledge compiled throughout history by early cultures. The current study has used literature from the 16 th to the 19 th centuries to assess reports that include accounts of Brazil's native plants, with possible reports of disorders of the Central Nervous System (CNS). Visits were paid to 27 institutions located in four Brazilian states. This resulted in raising 529 publications, out of which 65 were read, revealing that 33 of them contained reports of plants exerting effects on CNS ailments. These plants' scientific names underwent an updating process. The updating process resulted in 788 species names (129 correct scientific names and their 659 synonyms) out of which 66 hold current ethnopharmacology, pharmacology studies and/or patent application. Coincidences among past and present data have been observed in 46 cases. Only three of them carried applications for patents all of which coincided with past uses. There have hardly been any studies whatsoever throughout the centuries for many of the species currently being studied. Although of very seldom use, research in ethnopharmacology and historic literature can be promising tools for the selecting of new pharmaco products, further to contributing with retrieving traditional knowledge.

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Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos

Cited by 151 publications

References 74 publications

Adverse Neurodevelopmental Effects of Dexamethasone Modeled in PC12 Cells: Identifying the Critical Stages and Concentration Thresholds for the Targeting of Cell Acquisition, Differentiation and Viability

Adverse Neurodevelopmental Effects of Dexamethasone Modeled in PC12 Cells: Identifying the Critical Stages and Concentration Thresholds for the Targeting of Cell Acquisition, Differentiation and Viability

Comparative developmental neurotoxicity of organophosphates in vivo: Transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems

Brazilian plants with possible action on the central nervous system—A study of historical sources from the 16th to 19th century

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