Exposure to low doses of the environmental chemical dieldrin causes behavioral deficits in animals prevented from coping with stress

Carlson, Jeffrey; Rosellini, Robert A.

doi:10.1007/bf00690940

Cited by 15 publications

(5 citation statements)

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“…Both NR2A-and NR2B-containing NMDAR have a crucial role in cortical synaptic plasticity and memory (30,32). Therefore, the results presented here may contribute to our understanding of the molecular mechanisms underlying the cognitive and behavioral deficits found in animals after chronic exposure to this endocrine disruptor (12,13). In addition, the observed neuroprotective actions of allopregnanolone support its use as a potential therapeutic hormone against insults or neurodegenerative disorders in which GABAergic and/or glutamatergic systems are compromised.…”

Section: Discussionsupporting

confidence: 57%

“…We have previously reported that long-term exposure to dieldrin induces the internalization of the NMDAR in cerebellar granule cells and in cortical neurons as a consequence of permanent blockade of the GABA A R (10,11). These alterations may explain the cognitive and behavioral deficits observed in animals that are chronically exposed to dieldrin (12,13). However, the precise mechanisms underlying such impairments remain elusive.…”

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confidence: 99%

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Allopregnanolone Prevents Dieldrin-Induced NMDA Receptor Internalization and Neurotoxicity by Preserving GABAA Receptor Function

et al. 2012

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Dieldrin is an endocrine disruptor that accumulates in mammalian adipose tissue and brain. It induces convulsions due to its antagonism of the γ-aminobutyric acid A receptor (GABA(A)R). We have previously reported that long-term exposure to dieldrin causes the internalization of the N-methyl-D-aspartate receptor (NMDAR) as a result of persistent GABA(A)R inhibition. Because the neurosteroids 17β-estradiol (E2) and allopregnanolone are known to modulate the function and trafficking of GABA(A)R and NMDAR, we examined the effects of E2 and allopregnanolone on dieldrin-induced GABA(A)R inhibition, NMDAR internalization, and neuronal death in cortical neurons. We found that 1 nM E2 increased the membrane expression of NR1/NR2B receptors and postsynaptic density 95 but did not induce their physical association. In contrast, 10 nM E2 had no effect on these proteins but reduced NR2A membrane expression. We also found that exposure to 60 nM dieldrin for 6 d in vitro caused the internalization of NR1 and NR2B but not NR2A. Treatment with either 1 nM E2 or 10 μM allopregnanolone prevented the dieldrin-induced reduction in membrane levels of the NR1/NR2B receptors. Furthermore, prolonged exposure to 200 nM dieldrin down-regulated the expression of NR2A; this was inhibited only by allopregnanolone. Although both hormones restored NMDAR function, as measured by the NMDA-induced rise in intracellular calcium, allopregnanolone (but not E2) reversed the inhibition of GABA(A)R and neuronal death caused by prolonged exposure to dieldrin. Our results indicate that allopregnanolone protects cortical neurons against the neurotoxicity caused by long-term exposure to dieldrin by maintaining GABA(A)R and NMDAR functionality.

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Section: Discussionsupporting

confidence: 57%

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confidence: 99%

Allopregnanolone Prevents Dieldrin-Induced NMDA Receptor Internalization and Neurotoxicity by Preserving GABAA Receptor Function

et al. 2012

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“…Behavioral tests on rats treated with aldrin in utero showed the time for incisor teeth eruption was delayed and the time for testes descent increased. When rat pups became adults, they showed higher locomotor frequency measured by total number and duration of head-dips even when pesticide was not detected in the animal's tissue (157). Primary neuronal cultures of mesencephalic neurons from fetal rats and mice exposed to 7.98 µM of dieldrin showed a decrease in dopaminergic neurons and potential neurodegeneration (158).…”

Section: Soto Et Al (129) Discussed This Topicmentioning

confidence: 99%

Aldrin and dieldrin: a review of research on their production, environmental deposition and fate, bioaccumulation, toxicology, and epidemiology in the United States.

Jorgenson¹

2001

Environ Health Perspect

124

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In the last decade four international agreements have focused on a group of chemical substances known as persistent organic pollutants (POPs). Global agreement on the reduction and eventual elimination of these substances by banning their production and trade is a long-term goal. Negotiations for these agreements have focused on the need to correlate data from scientists working on soil and water sampling and air pollution monitoring. Toxicologists and epidemiologists have focused on wildlife and human health effects and understanding patterns of disease requires better access to these data. In the last 20 years, substantial databases have been created and now are becoming available on the Internet. This review is a detailed examination of 2 of the 12 POPs, aldrin and dieldrin, and how scientific groups identify and measure their effects. It draws on research findings from a variety of environmental monitoring networks in the United States. An overview of the ecologic and health effects of aldrin and dieldrin provides examples of how to streamline some of the programs and improve access to mutually useful scientific data. The research groups are located in many government departments, universities, and private organizations. Identifying databases can provide an "information accelerator" useful to a larger audience and can help build better plant and animal research models across scientific fields.

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“…A study in rats of the behavioural effects of low oral doses of dieldrin indicated that a single oral dose of 0.5 mg/kg bw can modify uncontrollable stress (Carlson and Rosellini, 1987). This is the study upon which the Dutch based their proposal for an ARfD.…”

Section: Neurotoxicitymentioning

confidence: 92%

“…The Dutch proposal for an ARfD was based upon a study of behavioural effects following oral exposure of rats to low doses of dieldrin (Carlson and Rosellini, 1987). The study indicated that dieldrin modified uncontrollable stress after a single oral dose of 0.5 mg/kg bw.…”

Section: Previously Derived Arfdsmentioning

confidence: 99%

Opinion of the Scientific Panel on Plant protection products and their Resi-dues on a request from the Commission on the risks associated with an in-crease of the MRL for dieldrin on courgettes

2007

EFSA Journal

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SUMMARYFollowing a request from the European Commission, the Panel on Plant Protection Products and their Residues (PPR Panel) was asked to deliver a scientific opinion on the risks associated with an increase of the MRL for dieldrin on courgettes.Dieldrin was developed in the 1940s and was widely used as an insecticide up to the early 1970s. However, its use was stopped when it became clear that it has very unfavourable environmental and toxicological characteristics. Today, dieldrin is therefore banned in most countries of the world. Moreover, it is on the list of the Stockholm Convention to protect human health and the environment from persistent organic pollutants.Dieldrin is very persistent in the environment and has a strong potential to accumulate in the food chain. Due to the very slow environmental degradation of the substance, dieldrin is still a widespread soil contaminant in Europe and other places. When growing courgettes on such soils, residues can be taken up by the plants and transported to the fruits. Monitoring data from The Netherlands show that courgettes grown in greenhouses from the western part of the country do not always comply with the existing MRL of 0.02 mg/kg. The Netherlands has therefore requested an increase of this MRL-value to 0.05 mg/kg and the European Commission has asked EFSA to evaluate the toxicological implications of the proposed new MRL-value.The main reasons for prohibiting the active substance were its environmental persistence and its tendency to accumulate in animal tissues. It is therefore appropriate to ask whether exposure as a result of eating courgettes with an increased MRL, together with other known sources of exposure (e.g. through animal products), represents a potential risk for European consumers in the long as well as in the short term.The residue definition for dieldrin under current EU residue guidelines specifies dieldrin "singly or combined with aldrin, expressed as dieldrin". This definition reflects the close chemical and toxicological relationship between these two cyclodiene insecticides. There are two isomers of dieldrin, the exo-and the endo-form. Dieldrin itself is the exo-isomer. The PPR Panel 2 briefly reviewed the characteristics of the different isomeric forms of dieldrin and concluded that focus should be on the exo-form of the substance, i.e. dieldrin itself. The Panel agreed not to include photodieldrin -an environmental product of dieldrin -in further consideration because this substance is not included in the residue definition. Furthermore photodieldrin has not been studied in such detail and the literature and data on the occurrence and fate of its residue are scarce.The Joint FAO/WHO Meeting on Pesticide Residues (JMPR) established an acceptable daily intake (ADI) for dieldrin in 1967, confirmed this in 1977 and converted (but not re-evaluated) it to a PTDI (Provisional Tolerable Daily Intake) in 1994. JMPR has not derived an acute reference dose (ARfD) for dieldrin. The propensity of dieldrin to accumulate in biological organisms...

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Exposure to low doses of the environmental chemical dieldrin causes behavioral deficits in animals prevented from coping with stress

Cited by 15 publications

References 15 publications

Allopregnanolone Prevents Dieldrin-Induced NMDA Receptor Internalization and Neurotoxicity by Preserving GABAA Receptor Function

Allopregnanolone Prevents Dieldrin-Induced NMDA Receptor Internalization and Neurotoxicity by Preserving GABAA Receptor Function

Aldrin and dieldrin: a review of research on their production, environmental deposition and fate, bioaccumulation, toxicology, and epidemiology in the United States.

Opinion of the Scientific Panel on Plant protection products and their Resi-dues on a request from the Commission on the risks associated with an in-crease of the MRL for dieldrin on courgettes

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