Chronic Low‐Level Lead Exposure Impairs Embryonic to Adult Conversion of the Neural Cell Adhesion Molecule

Abstract

The neural cell adhesion molecule (N-CAM) is a complex of surface glycoproteins that are developmentally regulated and believed to be intimately involved in the orderly structuring of the CNS. Here the effect of chronic low-level lead exposure on their expression in the postnatally developing cerebellum is described. Rat pups were chronically exposed to lead via their dam's drinking water which contained either 200 or 400 mg PbCl2/L from time of birth. Pup postnatal blood lead levels ranged between 10 and 20 micrograms/dl until day 16 after which they became elevated to 40 micrograms/dl on day 20. During this period the developmental sialylation state of N-CAM, which is believed to regulate cell-cell interaction, fibre outgrowth, and synapse formation, was monitored by rocket immunoelectrophoresis. In control animals the expected desialylation of N-CAM was found to occur at times coincident with postnatal synaptogenesis. In contrast, desialylation in animals chronically exposed to lead was found to be significantly impaired when blood lead levels exceeded 20 micrograms/dl. This could not be attributed to lead-induced undernutrition or alterations in immunoprecipitate formation. These observations could account for the neurobehavioural deficits that are known to be induced at similar blood lead levels, and the potential contribution of impaired N-CAM desialylation to synaptic elaboration is discussed.

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).…”

Prenatal low-level lead exposure and developmental delay of infants at age 6 months (Krakow inner city study)

“…These include effects on the hem biosynthesis, the nervous system, the kidneys and reproduction as well as on cardiovascular, hepatic, endocrinal and gastrointestinal functions. In conditions of low-level and long-term lead exposure, such as those found in the general population, the most critical effects are exerted on hem biosynthesis and the nervous system (Cookman et al, 1987;Freedman et al, 1990;Goyer, 1993;Juberg et al, 1997;Press, 1977). The cord blood concentration of lead represents the accumulated dose over the pregnancy period and to capture the early cognitive outcomes of lead exposure in the womb, we have chosen the Fagan test for measuring the intelligence of infants, which is a well recognized test of infant intelligence and has been found to be a predictor of later cognitive outcome Fagan et al, 1986;Fagan and Detterman, 1992).…”

The control of sialyltransferase activity in tumor‐cell lines derived from different tissues is multifactorial

“…In the embryonic nervous system in vivo, there is a developmentally-regulated decrease in sialyl-T activity which corresponds well with the onset of cell--cell adhesion and synaptogenesis [3,20,2 I] with subsequent alterations in the developmental expression of sialoglycoproteins causing an upset in neuronal patterning with consequent mental deficits [22,23]. Sialyl-T activity decreased significantly in parallel with the attainment of confluency in both the neuro-2A neuroblastma and C6 gtioma cell lines (Fig.…”