Animal Models of Cognitive Impairment Produced by Developmental Lead Exposure

Lead is probably the most-studied environmental contaminant with respect to the effects of developmental exposure on cognition in children or animal models. It has been known since the 1940s that lead poisoning in children can result in permanent behavioral sequelae, including poor school performance, impulsive behavior, and short attention span [1], that were observations later replicated by other investigators [2–4]. Early in the 1970s, deficits in intelligence quotient (IQ), fine motor performance, and behavioral disorders such as distractibility and constant need for attention were observed in children who had never exhibited overt signs of toxicity [5, 6]. In 1979 Needleman et al. [7] reported decreased IQ and increased incidence of distractibility and inattention in middle-class children who had not been exposed to lead from paint. Early studies of the effects of developmental exposure to lead in animals focused on determining deficits on a wide variety of tasks characterizing the constellation of the effects of lead [8]. Exposures in various studies included postnatal, lifetime, , or plus postnatal. Researchers also sought to identify a dose or body burden that did not produce adverse effects. A series of experiments with monkeys in our laboratory documented adverse effects in a group of monkeys with peak blood lead concentrations averaging 15 μg/dl during infancy, with steady-state levels over most of the lifespan averaging 11 μg/dl. Animals with lower body burdens have apparently not been assessed. The current CDC (Centers for Disease Control) “level of concern” is 10 μg/dl for children, although it is clear that there are adverse effects on cognition at blood concentrations below 10 μg/dl [9, 10]. More recently, experimental researchers have focused on developing paradigms to explore the behavioral mechanisms responsible for the constellation of effects observed in previous studies; these studies generally used doses that are known to produce robust impairment.