The effects of lead on the developing central nervous system of the rat.

Biochemical and structural development of the cerebral cortex of rat pups is delayed by low levels of lead administered in the dam's drinking water during gestation and suckling periods. These changes in brain development coincide with delays in the development of exploratory and locomotor activity and impaired learning. Subsequent cross-fostering experiments have shown that delays in synaptogenesis and in the development of exploratory behavior were attributed entirely to the prenatal, as opposed to the postnatal, exposure to lead at the low dose levels utilized. Examination of the variations in blood lead concentrations in pups and dams during gestation and until weaning at 21 days of postnatal age indicated that a substantial increase in blood lead concentrations occurred late in pregnancy. At 200 mg of Pb/liter of drinking water, peak blood Pb concentrations were observed to be approximately 60 micrograms/dl in dams and 80 micrograms/dl in pups on the 20th day of gestation. By the 10th postnatal day blood Pb concentrations had decreased to 35 micrograms/dl in dams and 40 microgram/dl in pups despite an increased consumption of drinking water containing the same concentration of Pb during this period. (Delays in cerebral cortical development were observed after 10 days of postnatal age). Tracer studies utilizing 203Pb indicate that the rate of Pb absorption was substantially increased in the pregnant, relative to the non-pregnant, dam. Although a similar increase in 45Ca absorption was also observed during pregnancy, increases in Pb absorption were enhanced by Pb-pretreatment, whereas Ca absorption was independent of Pb-pretreatment. From this data it is concluded that the apparently greater sensitivity of postnatal development on prenatal Pb exposure is secondary to enhanced Pb absorption in the pregnant rat. In vitro metabolic studies in isolated cerebral cortex slices taken from 15 day old rat pups exposed to Pb revealed increased glucose and oxygen consumption in response to elevations in the potassium concentration of the incubation media. This evidence of metabolic uncoupling in the immature rat cerebral cortex may be causally related to the measured delays in brain development.