ALTERED EXPRESSION OF POLYSIALYLATED NCAM IN MOUSE HIPPOCAMPUS FOLLOWING TRIMETHYLTIN ADMINISTRATION

Proper structuring of neural connections in the hippocampus is mediate d by cell adhesion molecules, membrane-linked proteins involved in cel l recognition and stabilization of cytoarchitecture. Modulated express ion of the neural cell adhesion molecule (NCAM) at the synapse permits plasticity required for both learning and memory. Polysialylation of NCAM, particularly the synapse-specific 180 kDa isoform (NCAM 180), al lows hippocampal neurons to alter their neuronal connections during le arning acquisition and memory consolidation in mature brain. These act ivity-dependent changes in NCAM expression represent a sensitive targe t for neurotoxicity. Trimethyltin (TMT) a potent hippocampal neurotoxi cant, alters total NCAM expression in whole mouse hippocampus and impa irs learning in rodents. To investigate the expression of polysialylat ed NCAM following TMT administration, Swiss-Webster mice were injected (i.p.) with 2.0 or 3.0 mg TMT/kg and sacrificed 6 hrs to 7 days later Immunocytochemical staining for polysialylated NCAM (PSA-NCAM) reveal ed marked reduction of staining of hippocampal dentate granule cells 6 -72 hours after TMT treatment. Partial recovery of hippocampal polysia lylated NCAM was observed after 7 days. lmmunoblot data indicated that loss of PSA-NCAM expression paralleled reductions seen in NCAM 180 an d markers of cytoskeletal integrity. Assays for proteolytic activity i n hippocampus revealed rapid, reversible protease activation which cor related temporally with the reduction of NCAM180 and PSA-NCAM. Proteol ytic degradation following hippocampal injury may serve to disrupt NCA M-mediated adhesion. Protracted loss of polysialylated NCAM in dentate gyrus following injury may serve as a useful marker in toxicant-induc ed learning disorders. (C) 1997 Intox Press, Inc.