A model of early life, brief episodic lead (Pb) exposure at <70mug/DI blood lead (PbB), superimposed on chronic Pb exposure at -35mug/dl for the first year and 14 mug/dl from then on, is being studied in the rhesus monkey (cohorts Pb IX and Pb X). Cohort controls are carried in parallel (<-5 mug/dl PbB. These PbB levels are relevant to human episodic plus chronic childhood lead exposure followed by PbB well below the action level. Monkeys exposed to high Pb pulse without Pb after the first year (PbIII) and thus at <5 mug/dl PbB from 3 years of age on, showed a permanent deficit on Delayed Spatial Alternation (DSA) tested as adults at 5-8 years of age (Levin & Bowman, 1986). Monkeys exposed only to chronic Pb levels for the first year (no pulse and no Pb after the first year; Pb II and Pb V), had a marginal DSA facilitation as adults (Levin et al, 1988). Monkeys exposed at 25 mug/dl PbB for 6 months, and chronic PbB of 13 mug/dl since, had a DSA deficit at 8 years of age (Rice, 1985). Chronic L-dopa treatment alleviated the DSA deficit in pulse-chronic animals (P? III) but cholinergic drugs had no effect (Levin & Bowman, 1987, 1988). Evidence suggests that these DSA effects (facilitation at lower dose-duration Pb exposure and deficits at higher dose-duration exposures) may be explained by sensory inattention resulting from damage to dopaminergic systems of the caudate nucleus, induced by Pb exposure during postnatal development in the monkey. Our latest data (on Pb IX and PB X) confirm that even without a high early Pb pulse, Pb exposure at 14 mug/dl following first year chronic Pb exposure as low as 40 mug/dl will induce a DSA deficit in the adolescent monkey. These animals will be tested longitudinally to confirm if the DSA deficit persists, and if so, whether it disappears with discontinuation of low level Pb dosing and decline of their PbB to <- mug/dl. If in the latter case the DSA deficit disappears, it will be restored by redosing with Pb. Then, studies of neurochemical mechanism will be resumed on this DSA deficit, to follow up mechanistic data on the Pb III (Levin & Bowman, 1987). In addition, attentional deficit, and if this correlates with the stages of DSA effects. Additionally, data indicating reduced turnover of brain norepinephrine associated with PbB levels, and to determine if other neurotransmitter effects are seen. To add replication and statistical power to the examination of all these relationships, an additional cohort of monkeys is proposed for Pb exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
3R01ES001062-15S1
Application #
3249475
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1978-05-01
Project End
1993-04-15
Budget Start
1992-04-01
Budget End
1993-04-15
Support Year
15
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Ferguson, S A; Kraemer, G W; Bowman, R E et al. (1993) Lack of effect of chronic developmental lead treatment on biogenic amines and metabolites in monkey cerebrospinal fluid. Neurotoxicol Teratol 15:229-35
Ferguson, S A; Medina, R O; Bowman, R E (1993) Home cage behavior and lead treatment in rhesus monkeys: a comparison with open-field behavior. Neurotoxicol Teratol 15:145-9
Levin, E D; Schantz, S L; Bowman, R E (1992) Use of the lesion model for examining toxicant effects on cognitive behavior. Neurotoxicol Teratol 14:131-41
Ferguson, S A; Bowman, R E (1992) Effects of arecoline and scopolamine on open field behavior of adult monkeys treated with lead during the first year postpartum. Neurotoxicol Teratol 14:73-80
Laughlin, N K; Bushnell, P J; Bowman, R E (1991) Lead exposure and diet: differential effects on social development in the rhesus monkey. Neurotoxicol Teratol 13:429-40
Ferguson, S A; Bowman, R E (1990) A nonhuman primate version of the open field test for use in behavioral toxicology and teratology. Neurotoxicol Teratol 12:477-81
Ferguson, S A; Bowman, R E (1990) Effects of postnatal lead exposure on open field behavior in monkeys. Neurotoxicol Teratol 12:91-7
Franks, P A; Laughlin, N K; Dierschke, D J et al. (1989) Effects of lead on luteal function in rhesus monkeys. Biol Reprod 41:1055-62
Levin, E D; Bowman, R E (1988) Long-term effects of chronic postnatal lead exposure on delayed spatial alternation in monkeys. Neurotoxicol Teratol 10:505-10
Levin, E D; Schneider, M L; Ferguson, S A et al. (1988) Behavioral effects of developmental lead exposure in rhesus monkeys. Dev Psychobiol 21:371-82

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