SELECTIVE LOSS OF THE 180-KDA FORM OF THE NEURAL CELL-ADHESION MOLECULE IN HIPPOCAMPUS AND CEREBELLUM OF THE ADULT-MOUSE FOLLOWING TRIMETHYLTIN ADMINISTRATION

The neural cell adhesion molecule (NCAM), a membrane glycoprotein whic h plays critical roles in cell-cell recognition and in the maintenance of cytoarchitecture in the adult brain, may be modulated in response to injury. To determine whether neurotoxic insult alters the profile o f NCAM expression, adult female Balb/c mice were given a single inject ion of trimethyltin chloride (TMT; 3.2 mg/kg ip) and killed 4 hr to 3 weeks later. Hippocampus and cerebellum were isolated and prepared for light microscopy or SDS-PAGE and immunoblot analysis using the monocl onal antibody 5B8, which recognizes the intracellular domains of the 1 40- and 180-kDa isoforms of NCAM. NCAM140 appeared unaffected in TMT-t reated mice at all time points. In contrast, decreased intensity of th e 180-kDa band was apparent in both hippocampus and cerebellum 4 hr af ter TMT administration; maximal loss of NCAM180 was seen in hippocampa l immunoblots 8 to 64 hr after treatment. The decrease in NCAM180 foll owed a similar but less pronounced course in cerebellum. Recovery of t he 180-kDa band in hippocampus and cerebellum was apparent around 64 h r and continued until NCAM180 of mice killed 3 weeks after treatment r esembled that of controls. No change in glial fibrillary acidic protei n was seen by immunoblot analysis, suggesting that the effect is selec tive for neurons. TMT-induced loss of NCAM180 may be a direct cytotoxi c effect, or may represent a reactive neuronal response to injurious s timuli. In either case, loss of NCAM180 accompanies cell injury follow ing toxicant exposure and may be related to cytoskeletal alterations a nd destabilization of cellular contacts. (C) 1994 Academic Press, Inc.