Developmental lead exposure disturbs expression of synaptic neural cell adhesion molecules in herring gull brains

Neurobehavioral testing of herring gull chicks (Larus argentatus) in both l aboratory and field studies indicates that lead exposure during critical pe riods of development causes neurological deficits that may compromise survi val in the wild. Accumulating evidence suggests that lead impairs neurodeve lopment, in part, by altering the expression of cell adhesion molecules (CA Ms) responsible for the proper formation and maintenance of neural structur e and synaptic function. We examined the adhesion molecules NCAM, L1, and N -cadherin in gull brains to determine whether these CAMs are altered by lea d exposure and might serve as markers of developmental neurotoxicity. One-d ay-old chicks were collected from nesting colonies and were laboratory hous ed. On post-hatching day (PHD) 2, chicks were given 100 mg/kg lead acetate or saline (intraperitoneally). Birds were killed on PHD 34, 44, or 55 (bloo d-lead levels averaged 27.4, 20.8, and 19.5 mu g/dl, respectively). Brains were removed and stored at -70 degrees C until analysis. Expression of CAMs was determined in synaptosomal preparations by Western blotting and the ac tivity of NCAM-associated sialyltransferase (ST) was determined in purified whole brain golgi apparatus. Elevation in synaptosomal polysialylated NCAM expression and a significant increase in golgi ST activity was observed in lead-treated animals at PHD 34. Reductions in synaptosomal N-cadherin were observed at PHD 34 and 44, while L1 expression appeared unaffected by lead at any timepoint. By 55 days post-hatching, no differences in N-cadherin e xpression, polysialylated NCAM expression or NCAM-associated ST activity we re seen in lead-treated animals as compared with age-matched control animal s. Lead-induced disruption of CAM expression during early neurodevelopment may contribute to behavioral deficits observed in herring gulls in both the laboratory and the field, and may serve as a marker for heavy metal exposu re during postnatal development. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.