Exposure to organophosphates reduces the expression of neurotrophic factors in neonatal rat brain regions: similarities and differences in the effects of chlorpyrifos and diazinon on the fibroblast growth factor superfamily.
BACKGROUND: The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. OBJECTIVES: We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal...
| Publicado en: | Environmental Health Perspectives Vol. 115; no. 6; pp. 909 - 917 |
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| Autores principales: | , , |
| Formato: | research Journal Article |
| Publicado: |
National Institute of Environmental Health Sciences
Jun2007
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105847652&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105847652 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Jun2007 vid: 115 iid: 6 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 105847652 105847652 105847651 10.1289/ehp.9901 NLM17589599 105847652 ppf: 909 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Exposure to organophosphates reduces the expression of neurotrophic factors in neonatal rat brain regions: similarities and differences in the effects of chlorpyrifos and diazinon on the fibroblast growth factor superfamily. aug: au: Slotkin TA Seidler FJ Fumagalli F affil: Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA sug: subj: Brain Metabolism Genes Drug Effects Growth Substances Metabolism Insecticides Analysis of Variance Animals Biochips Dose-Response Relationship, Drug Organothiophosphorus Compounds Rats Animal Studies ab: BACKGROUND: The fibroblast growth factor (FGF) superfamily of neurotrophic factors plays critical roles in neural cell development, brain assembly, and recovery from neuronal injury. OBJECTIVES: We administered two organophosphate pesticides, chlorpyrifos and diazinon, to neonatal rats on postnatal days 1-4, using doses below the threshold for systemic toxicity or growth impairment, and spanning the threshold for barely detectable cholinesterase inhibition: 1 mg/kg/day chlorpyrifos and 1 or 2 mg/kg/day diazinon. METHODS: Using microarrays, we then examined the regional expression of mRNAs encoding the FGFs and their receptors (FGFRs) in the forebrain and brain stem. RESULTS: Chlorpyrifos and diazinon both markedly suppressed fgf20 expression in the forebrain and fgf2 in the brain stem, while elevating brain stem fgfr4 and evoking a small deficit in brain stem fgf22. However, they differed in that the effects on fgf2 and fgfr4 were significantly larger for diazinon, and the two agents also showed dissimilar, smaller effects on fgf11, fgf14, and fgfr1. CONCLUSIONS: The fact that there are similarities but also notable disparities in the responses to chlorpyrifos and diazinon, and that robust effects were seen even at doses that do not inhibit cholinesterase, supports the idea that organophosphates differ in their propensity to elicit developmental neurotoxicity, unrelated to their anticholinesterase activity. Effects on neurotrophic factors provide a mechanistic link between organophosphate injury to developing neurons and the eventual, adverse neurodevelopmental outcomes. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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