Effects of chronic developmental lead exposure on monkey neuroanatomy: Visual system

Reuhl, Kenneth R.; Rice, Deborah C.; Gilbert, Steven G.; Mallett, Joan E.

doi:10.1016/0041-008x(89)90157-9

Cited by 30 publications

(8 citation statements)

References 27 publications

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“…The effect of lead on neuronal morphology that we and others (40)(41)(42)(43)(44)(45) observe may be due to impaired assembly or stability of the cytoskeleton (46). Our interpretation is consistent with the ability of lead to interfere with calciumdependent events (47) including calcium-sensitive protein kinases (48)(49)(50), which have been implicated in neuronal growth in a variety of neurons (51)(52)(53)(54), including frog retinal axons (38,55).…”

Section: Discussionsupporting

confidence: 76%

Low lead levels stunt neuronal growth in a reversible manner.

Cline

Witte

Jones

1996

Proc. Natl. Acad. Sci. U.S.A.

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The developing brain is particularly susceptible to lead toxicity; however, the cellular effects of lead on neuronal development are not well understood. The effect of exposure to nanomolar concentrations of lead on several parameters of the developing retinotectal system of frog tadpoles was tested. Lead severely reduced the area and branchtip number of retinal ganglion cell axon arborizations within the optic tectum at submicromolar concentrations. These effects of lead on neuronal growth are more dramatic and occur at lower exposure levels than previously reported.Lead exposure did not interfere with the development of retinotectal topography. The deficient neuronal growth does not appear to be secondary to impaired synaptic transmission, because concentrations of lead that stunted neuronal growth were lower than those required to block synaptic transmission. Subsequent treatment of lead-exposed animals with the chelating agent 2,3-dimercaptosuccinic acid completely reversed the effect of lead on neuronal growth. These studies indicate that impaired neuronal growth may be responsible in part for lead-induced cognitive deficits and that chelator treatment counteracts this effect.Children exposed to lead, even at concentrations that were once considered low, have learning disabilities and behavioral problems (1-3), including deficits in visual system function (4, 5). Two of the major questions regarding lead toxicity concern the limits of exposure that cause neurological damage in children and the reversibility of the damage following transient exposure to lead. The Centers for Disease Control (6) recently lowered the level of blood lead considered harmful to 10 ,ug per 100 ml of blood (0.48 MiM); however, the issue of a threshold level for lead neurotoxicity remains controversial (7,8).Calcium disodium-EDTA, a commonly used chelation agent, reportedly causes a redistribution of lead to the brain (9). This does not occur following treatment with 2,3-dimercaptosuccinic acid (DMSA; ref. 10), an orally active lead chelating agent, which recently received Food and Drug Administration approval. Although DMSA lowers body lead burden (11-13), its ability to ameliorate behavioral deficits in lead-exposed children has not been demonstrated. DMSA is currently the subject of a double blind clinical study to test its ability to reverse the effect of lead on cognitive function.We tested the effect of lead exposure in nanomolar concentrations on the following aspects of the development of the visual projection in frogs: neuronal growth, synaptic transmission, and the maintenance of topographic retinotectal projections. We also assessed the ability of the chelating agent DMSA to reverse the effect of lead exposure on neuronal growth and compared this to the effect of simply removing the lead source from the animal. MATERIALS AND METHODSElvax Preparation and Surgical Implantation. Elvax was prepared and implanted over the optic tectum of Rana pipiens tadpoles as described (14). Elvax40P (DuPont) was prepared with stock...

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Section: Discussionsupporting

confidence: 76%

Low lead levels stunt neuronal growth in a reversible manner.

Cline

Witte

Jones

1996

Proc. Natl. Acad. Sci. U.S.A.

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“…Retinal damage has been associated with exposure to a wide range of toxins including several heavy metals (Merigan & Weiss, 1980;Mulak, 1998) and organic solvents (Mergler, Blain, & Lagace, 1987). Low-level lead exposure is known to cause visual deficits in rats and monkeys, affecting both the retina and the visual cortex (Bushnell, Bowman, Allen, & Marlar, 1977;Otto & Fox, 1993;Reuhl, Rice, Gilbert, & Mallett, 1989;Winneke, Brockhaus, & Baltissen, 1977). The proposed mechanism for many of these effects is an alteration in retinal DA (Shulman, Kala, Jadhav, & Fox, 1996).…”

Section: Lead Exposure and Color Visionmentioning

confidence: 97%

Low-Level Lead Exposure, Executive Functioning, and Learning in Early Childhood

Canfield¹,

Kreher²,

Cornwell³

et al. 2003

Child Neuropsychology

117

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The current paper presents evidence relating low-level lead exposure to impaired executive functioning in young children. Using the Shape School task, we assessed focused attention, attention switching, working memory, and the ability to inhibit automatic responses in a cohort of 170 children. Participants performed the Shape School task at both 48 and 54 months of age; the mean blood lead level was 6.49 microg/dl at 48 months. After controlling for a wide range of sociodemographic, prenatal, and perinatal variables, blood lead level was negatively associated with children's focused attention while performing the tasks, efficiency at naming colors, and inhibition of automatic responding. In addition, children with higher blood lead levels completed fewer phases of the task and knew fewer color and shape names. There was no association between blood lead and performance on the most difficult tasks, those requiring attention switching or the combination of inhibition and switching. Children's IQ scores were strongly associated with blood lead and Shape School performance, and when entered as a covariate, only color knowledge and the number of tasks completed remained significant. Results provide only weak support for impaired executive functioning, but the deficits in color knowledge may indicate a primary sensory deficit or difficulty with forming conditional associations, both implicating disruptions in dopamine system function.

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“…Reductions in dopaminergic activity have been observed in Pb 2+ -exposed animals (Tavakoli-Nezhad et al, 2001) and have been related to l l alterations in tyrosine hydroxylase activity (Jadhav and Ramesh, 1997). Early studies indicate that moderate lead exposure has long term repercussions on the cholinergic visual system of adult rats (Costa and Fox, 1983) and primates (Reuhl et al, 1989), while more recent studies demonstrate developmental cholinotoxicity following low-level Pb 2+ exposure, resulting in a persisting deficit in hippocampal cholinergic innervation (Bourjeily and Suszkiw, 1997). Expression of acetylcholinesterase and the acetylcholine receptor were also reduced in isolated tissue from neural retina of embryonic chick after in vitro Pb 2+ treatment (Luo and Berman, 1997).…”

Section: Introductionmentioning

confidence: 95%

Molecular targets of lead in brain neurotoxicity

Marchetti

2003

neurotox res

151

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The detrimental effects of lead poisoning have been well known since ancient times, but some of the most severe consequences of exposure to this metal have only been described recently. Lead [Pb(II)] affects the higher functions of the central nervous system and undermines brain growth, preventing the correct development of cognitive and behavioral functions. As an established neurotoxin, Pb(II) crosses the blood-brain barrier rapidly and concentrates in the brain. The mechanisms of lead neurotoxicity are complex and still not fully understood, but recent findings recognized that both Ca(II) dependent proteins and neurotransmitters receptors represent significant targets for Pb(II). In particular, acute and chronic exposure to lead would predominantly affect two specific protein complexes: protein kinase C and the N-methyl-D-aspartate subtype of glutamate receptor. These protein complexes are deeply involved in learning and cognitive functions and are also thought to interact significantly with each other to mediate these functions. This review outlines the most recent hypotheses and evidences that link lead poisoning to impairment of these protein functions, as well as the in vitro experimental approaches that are most likely to provide information on basic mechanicistic processes.

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Effects of chronic developmental lead exposure on monkey neuroanatomy: Visual system

Cited by 30 publications

References 27 publications

Low lead levels stunt neuronal growth in a reversible manner.

Low lead levels stunt neuronal growth in a reversible manner.

Low-Level Lead Exposure, Executive Functioning, and Learning in Early Childhood

Molecular targets of lead in brain neurotoxicity

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