Behavioral indicators of lead neurotoxicity: Results of a clinical field survey

At picomolar concentrations, lead activates protein kinase C (PKC). This activation has been implicated in the neurotoxicity of lead. No prior study has evaluated the association of PKC activity with neurobehavioral function in humans. The purpose of this study was to determine whether PKC activity is associated with neurobehavioral function or modifies the relationship between blood lead levels and neurobehavioral test scores. In this cross-sectional study of 212 current lead workers in the Republic of Korea, we assessed blood lead levels, neurobehavioral test scores, and PKC activity. PKC activity was determined by measuring the levels of phosphorylation of three erythrocyte membrane proteins (spectrin and the 52-kDa and 48-kDa subunits of band 4.9), using an in vitro back-phosphorylation assay. When linear regression was used to control for confounding variables, blood lead was a significant predictor of decrements in performance on tests of psychomotor function, manual dexterity, and executive ability. In linear regression models, back-phosphorylation levels were not associated with neurobehavioral test scores, but when dichotomized at the median, back-phosphorylation levels modified the relationship between blood lead and test scores. For spectrin and the 52-kDa and 48-kDa subunits of band 4.9, 5, 2, and 5 of 14 interaction terms, respectively, had associated p-values less than 0.10, all with positive signs, indicating that blood lead was associated with worse test scores only in subjects with lower back-phosphorylation levels. These data indicate that blood lead levels are associated with decrements in neurobehavioral test scores, mainly in the domains of manual dexterity and psychomotor function, but only in subjects with lower in vitro back-phosphorylation levels, which is equivalent to higher in vivo PKC activity. We hypothesize that subjects with higher PKC activity in the presence of lead may be more susceptible to the health effects of lead.

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“…These observations are consistent with those of earlier cross-sectional studies of occupationally exposed subjects (50)(51)(52)(53)(54).…”

Section: Discussionsupporting

confidence: 93%

Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers.

Hwang

Lee

Bressler

et al. 2002

Environ Health Perspect

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“…Less severe neurologic and behavioral effects have been documented in lead-exposed workers with BPb levels between 40 and 120 µg/dL. Evidence consistently indicates that lead-exposed workers perform worse on tests of visual motor functioning, reaction time, memory, attention, and concentration, with effects on mood also often being noted (Arnvig et al 1980;Baker et al 1984;Campara et al 1984;Grandjean et al 1978;Haenninen et al 1978;Hogstedt et al 1983;Schwartz et al 2001;Stollery 1996;Stollery et al 1991;Valciukas et al 1978).…”

Section: Discussionmentioning

confidence: 99%

Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning.

Weisskopf

Mulkern

et al. 2004

Environ Health Perspect

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Seventy-one-year-old identical twin brothers with chronic lead poisoning were identified from an occupational medicine clinic roster. Both were retired painters, but one brother (J.G.) primarily removed paint and had a history of higher chronic lead exposure. Patella and tibia bone lead concentrations measured by K-X-ray fluorescence in each brother were 5-10 times those of the general population and about 2.5 times higher in J.G. than in his brother (E.G.). Magnetic resonance spectroscopy (MRS) studies examined N-acetylaspartate:creatine ratios, a marker of neuronal density. Ratios were lower in J.G. than in his brother. Scores on neurocognitive tests that assess working memory/executive function were below expectation in both twins. Short-term memory function was dramatically worse in J.G. than in his brother. These results demonstrate some of the more subtle long-term neurologic effects of chronic lead poisoning in adults. In particular, they suggest the presence of frontal lobe dysfunction in both twins, but more dramatic hippocampal dysfunction in the brother with higher lead exposure. The MRS findings are consistent with the hypothesis that chronic lead exposure caused neuronal loss, which may contribute to the impairment in cognitive function. Although a causal relation cannot be inferred, the brothers were genetically identical, with similar life experiences. Although these results are promising, further study is necessary to determine whether MRS findings correlate both with markers of lead exposure and tests of cognitive function. Nevertheless, the results point to the potential utility of MRS in determining mechanisms of neurotoxicity not only for lead but also for other neurotoxicants as well.

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“…A similar study, however, reported no differences in arousal, reaction time, or grip strength between a reference group (mean PbB, 28 μg/dL) and workers who had been exposed to lead for 12±9.5 years (mean PbB, 61 μg/dL) (Milburn et al 1976); however, the relatively high mean PbB in the referents may have obscured the results. Disturbances in reaction time, visual motor performance, hand dexterity, IQ test and cognitive performance, nervousness, mood, or coping ability were observed in lead workers with PbBs of 50-80 μg/dL (Arnvig et al 1980;Haenninen et al 1978;Hogstedt et al 1983;Mantere et al 1982;Valciukas et al 1978). Baker et al (1983) reported impaired verbal concept formation, memory, and visual/motor performance among workers with PbB >40 μg/dL.…”

Section: Health Effectsmentioning

confidence: 99%

Characterizing Golden Eagle Risk to Lead and Anticoagulant Rodenticide Exposure: A Review

Herring

Eagles‐Smith

Buck

2017

Journal of Raptor Research

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Behavioral indicators of lead neurotoxicity: Results of a clinical field survey

Cited by 97 publications

References 25 publications

Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers.

Protein kinase C activity and the relations between blood lead and neurobehavioral function in lead workers.

Cognitive deficits and magnetic resonance spectroscopy in adult monozygotic twins with lead poisoning.

Characterizing Golden Eagle Risk to Lead and Anticoagulant Rodenticide Exposure: A Review

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