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 which 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 of NCAM expression, adult female Balb/c mice were given a single injection 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 monoclonal antibody 5B8, which recognizes the intracellular domains of the 140- and 180-kDa isoforms of NCAM. NCAM140 appeared unaffected in TMT-treated mice at all time points. In contrast, decreased intensity of the 180-kDa band was apparent in both hippocampus and cerebellum 4 hr after TMT administration; maximal loss of NCAM180 was seen in hippocampal immunoblots 8 to 64 hr after treatment. The decrease in NCAM180 followed a similar but less pronounced course in cerebellum. Recovery of the 180-kDa band in hippocampus and cerebellum was apparent around 64 hr and continued until NCAM180 of mice killed 3 weeks after treatment resembled that of controls. No change in glial fibrillary acidic protein was seen by immunoblot analysis, suggesting that the effect is selective for neurons. TMT-induced loss of NCAM180 may be a direct cytotoxic effect, or may represent a reactive neuronal response to injurious stimuli. In either case, loss of NCAM180 accompanies cell injury following toxicant exposure and may be related to cytoskeletal alterations and destabilization of cellular contacts.
Dey
P M
PM
Neurotoxicology Laboratories, Rutgers University, College of Pharmacy, Piscataway, New Jersey 08854-0789.
Graff
R D
RD
Lagunowich
L A
LA
Reuhl
K R
KR
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D051379:Mice; D008807:Mice, Inbred BALB C; D008853:Microscopy; D014298:Trimethyltin Compounds / Q000633:toxicity*
D015816:Cell Adhesion Molecules, Neuronal; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride