Effect of lead on Na+,K+ ATPase activity in the developing brain of intra-uterine growth-retarded rats

Lead (Pb) intoxication in developing mammals, including humans, produces serious brain damage. In addition, it is known that nutritional status influences the susceptibility to Pb toxicity. We developed anin utero undernutrition model based on restriction of blood supply to fetuses on d 17 of pregnancy (IUGR rats). The aim of this study was to investigate in vitro the possible effect of Pb on Na⁺,K⁺ ATPase activity in the brain of developing IUGR and control rats from 6 to 60 d after birth. In addition, we measured the stimulation of Na⁺,K⁺ ATPase by the monoamines noradrenaline and serotonin. Our results show that: (1) The neurotoxic effect of Pb is an age-related phenomenon. Both IUGR and control rats were more sensitive to Pb in the first week of life. In adults, Pb had a weak inhibitory potency; (2) the delayed matured brain in IUGR animals seemed less sensitive to Pb when compared to age-paired control rats; (3) in the IUGR group, at 15 and 22 d, low doses of Pb had a stimulatory effect on Na⁺,K⁺ ATPase instead of an inhibitory effect; (4) noradrenaline and serotonin stimulated Na⁺,K⁺ ATPase activity to an equivalent extent, but this was greater in IUGR than control rats; and (5) at low Pb concentrations, the studied monoamines reversed Pb-induced inhibition.