The Effects of Chronic Low-level Lead Exposure on the Early Structuring of the Central Nervous System

Regan, Ciaran M.; Cookman, Gillian R.; Keane, Gary; King, William; Hemmens, Susan E.

doi:10.1007/978-94-009-0847-5_29

Lead Exposure and Child Development 1989

DOI: 10.1007/978-94-009-0847-5_29

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The Effects of Chronic Low-level Lead Exposure on the Early Structuring of the Central Nervous System

Ciaran M. Regan¹,

Gillian R. Cookman²,

Gary Keane³

et al.

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1989

1997

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Cited by 3 publications

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“…The high sensitivity of the fetus to the toxic effects of lead has been ascribed to the poorly developed blood:brain barrier (Goyer, 1990) and to the potential susceptibility of the developing nervous system during early structuring and modification of the neuronal circuitry (Regan et al, 1989). Hence, a greater understanding of the mobilization of lead from bone to blood during pregnancy is desirable (Mushak, 1993;Franklin et al, 1995).…”

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confidence: 99%

Use of Sequentially Administered Stable Lead Isotopes to Investigate Changes in Blood Lead during Pregnancy in a Nonhuman Primate (Macaca fascicularis)

et al. 1997

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The effects of pregnancy on the flux of lead from maternal bone were investigated in five females from a unique colony of cynomolgus monkeys (Macaca fascicularis) which had been dosed orally with lead (approximately 1100-1300 /ig Pb/kg body wt) throughout their lives (about 14 years). Through the use of stable lead isotopes ^Pb, ^Pb, and ^Pb, it was possible to differentiate between the lead contributed to blood lead from the skeleton and the lead contributed from the current oral dose. Blood samples and bone biopsy samples taken before, during, and after pregnancy were analyzed for lead (total and stable isotope ratios) by thermal lonization mass spectrometry. Through the use of end-member unmixing equations, the contribution to blood of lead from maternal bone during pregnancy was estimated and compared to the contribution of lead from maternal bone before pregnancy. A 29 to 56% decrease in bone lead mobilization in the first trimester was followed by an increase in the second and third trimesters, up to 44% over baseline levels. In one monkey, the third-trimester increase did not reach baseline levels. In a single low-lead monkey, a similar decrease in the first trimester was followed by a 60% increase in the third trimester, indicating that a similar pattern of flux is seen over a wide range of lead concentrations. Analysis of maternal bone and fetal bone, brain, liver, and kidneys confirmed a substantial transplacental transfer of endogenous lead. Lead concentrations in fetal bone often exceeded maternal bone lead concentrations. From 7 to 39% of the lead in the fetal skeleton originated from the maternal skeleton, o 1977 society of Toxicology.Lead is a ubiquitous metal that continues to be of significant public health concern despite decades of study and regu-

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confidence: 99%

Use of Sequentially Administered Stable Lead Isotopes to Investigate Changes in Blood Lead during Pregnancy in a Nonhuman Primate (Macaca fascicularis)

et al. 1997

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The effect of low level lead exposure on the postnatal structuring of the rat cerebellum

Hasan¹,

Cookman²,

Keane³

et al. 1989

Neurotoxicology and Teratology

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Lead‐induced developmental changes in AP‐1 DNA binding in rat brain

Pennypacker

Xiao

et al. 1997

Intl J of Devlp Neuroscience

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Exposure to lead during ontogeny is detrimental to the growth and development of the brain. Morphological abnormalities occur in the developing brain, which are manifested as mental retardation and other neurological disorders. Despite extensive research, the biochemical mechanism for neurological effects of lead has not been established but appears to be at the level of the genome since aberrant expression of developmentally-important genes has been reported. Basal levels of activator protein 1 (AP-1) transcription factor DNA binding are elevated in the rat brain during the early postnatal period. The AP-1 DNA binding complex is composed of a Jun:cAMP responsive element binding protein dimer, which appears to modulate expression of developmentally-important genes that contain AP-1 binding sites in their promoter. Brain regions from perinatally lead-exposed rats were examined on postnatal days 3, 9 and 15 for DNA binding activity to the AP-1 DNA sequence. AP-1 DNA binding activities were significantly increased on postnatal day 3 in hippocampus and cortex from lead-treated rats with no other area (frontal lobe or brainstem) or timepoint showing significant changes. Since no increases were detected in the level of Jun protein which is a component of the AP-1 binding complex, post-translational modification may be involved in enhancing DNA binding activity. By altering levels of AP-1 DNA binding to the promoter regions, lead exposure may be changing the levels of mRNA synthesis of developmentally important genes.

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The Effects of Chronic Low-level Lead Exposure on the Early Structuring of the Central Nervous System

Cited by 3 publications

References 28 publications

Use of Sequentially Administered Stable Lead Isotopes to Investigate Changes in Blood Lead during Pregnancy in a Nonhuman Primate (Macaca fascicularis)

Use of Sequentially Administered Stable Lead Isotopes to Investigate Changes in Blood Lead during Pregnancy in a Nonhuman Primate (Macaca fascicularis)

The effect of low level lead exposure on the postnatal structuring of the rat cerebellum

Lead‐induced developmental changes in AP‐1 DNA binding in rat brain

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