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We investigated the effect of 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) on the expression of synaptic proteins in dissociated E18 rat cortical cells. TCDD (0-50 nM) was added to plating media, and cell viabil-ity and expression of synaptic proteins were assayed on 4 and 7 days in vitro (DIV), respectively. TCDD had no apparent effect on early neurite outgrowth 12 h after plating. However, on 4 DIV, cell viability was re-duced significantly, and neurons often revealed vacu-oles in 20 or 50 nM culture and had limited secondary or higher order dendritic processes in 20 or 50 nM culture. Immunoblot analyses of cell homogenates in-dicated upregulation of NMDA receptor subunits (NR1, NR2A, and NR2B), but downregulation of syn-aptic organizing proteins (PSD-95, densin-180, and septin6 homologue) and a synapse-enriched enzyme (aCaMKII). Changes in the expression of synaptic proteins may be a underlying mechanism for altered synaptic transmission and neuropathy by TCDD.