Neonatal lead exposure impairs development of rodent barrel field cortex

Abstract

Childhood exposure to low-level lead can permanently reduce intelligence, but the neurobiologic mechanism for this effect is unknown. We examined the impact of lead exposure on the development of cortical columns, using the rodent barrel field as a model. In all areas of mammalian neocortex, cortical columns constitute a fundamental structural unit subserving information processing. Barrel field cortex contains columnar processing units with distinct clusters of layer IV neurons that receive sensory input from individual whiskers. In this study, rat pups were exposed to 0, 0.2, 1, 1.5, or 2 g͞liter lead acetate in their dam's drinking water from birth through postnatal day 10. This treatment, which coincides with the development of segregated columns in the barrel field, produced blood lead concentrations from 1 to 31 g͞dl. On postnatal day 10, the area of the barrel field and of individual barrels was measured. A dose-related reduction in barrel field area was observed (Pearson correlation ‫؍‬ ؊0.740; P < 0.001); mean barrel field area in the highest exposure group was decreased 12% versus controls. Individual barrels in the physiologically more active caudoventral group were affected preferentially. Total cortical area measured in the same sections was not altered significantly by lead exposure. These data support the hypothesis that lead exposure may impair the development of columnar processing units in immature neocortex. We demonstrate that low levels of blood lead, in the range seen in many impoverished inner-city children, cause structural alterations in a neocortical somatosensory map.

Learning, Memory, and Transcription Factors

“…The Aarskog or faciogenital dysplasia syndrome and nonsyndromic mental retardation resulting from mutations in p21-activated kinase 3 (PAK3) are also due to disorders in pathways related to Ras activation (53). A similar mechanism may contribute to cognitive impairment in children exposed to environmental lead, inasmuch as this toxin can activate PKC, which in turn can enhance Ras activity (54,55). It seems probable that additional cognitive disorders in children will be linked to defects in these pathways.…”

The relationship between lead in plasma and whole blood in women.

“…However, many individuals continue to suffer elevated exposures from environmental and occupational sources, and possibly from the mobilization of skeletal body stores accumulated over previous periods of elevated exposures (1)(2)(3)(4). The potential impact of mobilized skeletal Pb stores on the developing fetus in pregnant women has been of particular concern because laboratory and epidemiologic data have indicated that the developing nervous system is especially sensitive to perturbations with Pb (5)(6)(7).…”

Impact of Some Heavy Metals Toxicity on Behaviour, Biochemical and Histopathological Alterations in Adult Rats

“…After an acclimatization period of one week, the rats were randomly assigned into five groups (five rats each), two groups treated with lead acetate which were, GA (low lead acetate), that was given 1g/l lead acetate and GB (high lead acetate), which was treated with 2 g/l lead acetate in drinking water (Wilson et al, 2000). However, the other two groups were treated with anhydrous aluminium chloride, that were GC (low aluminium chloride), which admistered 2 g/l anhydrous aluminum chloride (Gromysz-Kalkowska et al, 2004) and GD (high aluminium chloride) that was given 3.5 g/l anhydrous aluminium chloride in drinking water (Misawa and Shigeta, 1992).…”