The effect of prenatal and postnatal lead exposure on neonatal synaptogenesis in rat cerebral cortex

Abstract

Pregnant rats were exposed to drinking water with lead (Pb) concentrations of 0, 30, or 200 mg/l. The resultant pups were sacrificed at 11, 15, and 21 d of postnatal age for the determination of synapses/mm3 in parietal cortex. Synaptic counts from electron micrographs of ethanol phosphotungstic acid stained cortical slices were counted by four observers who were blinded as to treatment (control or 200 mg Pb/l drinking water). A greater than fourfold increase in synaptic counts was observed in layers I, II, and III of rat pups parietal cortex between 11 and 21 d of age. Pb treatment depressed synaptic counts maximally at 15 d of age. However, Pb-exposed pups displayed essentially the same synaptic counts as controls by 21 d of age. In a cross-fostering design, it was shown that prenatal exposure to Pb completely accounted for the delays in synaptogenesis. No significant depression of synaptic counts was observed in pups exposed only during the postnatal period. Blood lead concentrations (Pb X B) were determined during gestation and suckling in both mother and offspring. A dramatic peripartum (partum plus and minus 4 d) peak in Pb X B was seen in mother and pup. Pup Pb X B peaked at 80 micrograms/dl at exposures of 200 mg Pb/l drinking water. In addition to being dose-dependent, blood Pb levels resulting from the same concentration of Pb in drinking water displayed a significant dependence on litter at time-points between birth and 1 yr of age. These data indicate that the substantially elevated blood Pb concentrations that are evident at partum in pups prenatally exposed to Pb might be responsible for the postnatally observed delay in synaptogenesis.

Low-level lead exposure triggers neuronal apoptosis in the developing mouse brain

“…In vitro evidence of an apoptosis in PC 12 cells has been identified by an increase in BAX and activation of caspase-3 (Xu et al, 2006), but the exact mechanism of neurotoxicity remains largely unknown. Several mechanisms of lead neurotoxicity have been proposed: 1) vasculopathy resulting in breakdown of the blood brain barrier, intracranial hemorrhage and/or cerebral edema (Lorenzo et al 1978; Struzynska et al, 1997); 2) modification of synaptogenesis (McCauley et al, 1982); 3) disruptions of energy metabolism, calcium homeostasis, and cell signaling (Busselberg 1995; Goldstein 1993; Simons 1993) and 4) alterations in neurotransmitter systems, particularly the glutamatergic system and its effects at N-methly-D-aspartate (NMDA) glutamate receptors (Carpenter et al 1994; Guilarte et al, 1997; Guilarte and McGlothan, 2003; Guilarte and Miceli, 1992; Schulte et al, 1995). …”

Workshop to identify critical windows of exposure for children's health: neurobehavioral work group summary.

“…Effects on gross brain structure have not been evident in studies directed at understanding underlying neuropathology associated with low-level lead exposure. Instead, the effects most consistently noted are those on synaptogenesis and dendritic arborization (42)(43)(44)(45)(46), in vivo physiological examinations of synaptic plasticity (47)(48)(49), and decrements in myelination (50,51). Changes in glutamate and y-aminobutyric acid synthesis and release (52,53) and the glutamate N-methyl-Daspartate (NMDA) receptor levels and binding affinities have also been reported in association with low-level lead exposure (54).…”

Adverse Outcome Pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities

“…: Elevated blood Pb2+ concentrations that have been evident in new-born rats prenatally exposed to 30 or 200 mg/l Pb2+ caused postnatally delay in synaptogenesis (McCauley et al, 1982). In this study, Pb2+ treatment depresses synaptic counts in pups of PND 11 to 15 but not in older pups (McCauley et al, 1982).…”

“…In this study, Pb2+ treatment depresses synaptic counts in pups of PND 11 to 15 but not in older pups (McCauley et al, 1982). In rat hippocampal primary cultures, Pb2+ treatment has no effect on PSD95 puncta density nor has any effect on Synapsin Ia/b total gray value, puncta density, and integrated intensity but only reduces the phosphorylation of Synapsin Ia/b .…”