AN ANTIBODY TO NEURAL CELL-ADHESION MOLECULE IMPAIRS MOTOR-NERVE TERMINAL SPROUTING IN A MOUSE MUSCLE LOCALLY PARALYZED WITH BOTULINUM TOXIN

We have investigated the possible role of neural cell adhesion molecule, in promoting motor nerve terminal sprouting in the paralysed mouse gluteus maximus muscle, using a rabbit polyclonal antiserum to mouse brain neural cell adhesion molecule (donated by Dr C. Goridis). This antiserum recognizes neural cell adhesion molecule in the basal lamina and extracellular matrix of denervated mouse muscles (1988, Booth C. M. and Brown M. C., Neuroscience 27, 699-709). As a single dose of antibody injected in vivo over the surface of denervated gluteal muscles bound for 12-48 h to over 80% of fibres expressing neural cell-adhesion molecule, once daily injections were used to see if there was any action on terminal sprouting. Injections of antibody were made for four days, starting three days after muscles were paralysed with botulinum toxin. To avoid non-specific complement-mediated attack on neural cell adhesion molecule bearing motor nerve terminals, mice of the DBA/2 strain were used as these lack complement component C5. They were further complement depleted by daily intraperitoneal injections of colloidal inulin. The percentage of end plates bearing terminal sprouts (visualized in whole mounts of the gluteus maximus with zinc iodide-osmium staining) was reduced from a mean of 60.5% ± 3.2 (n = 11) for mice treated with botulinum toxin alone and 61.5% ± 1.2 (n = 8) for those treated with non-immune serum, to 37.3% + 3.6 (n = 8) in the anti-neural cell adhesion molecule injected series. In addition the anti-neural cell adhesion molecule treated material showed a higher proportion of shorter sprouts than the two control groups. A polyclonal antibody to Thy-1 (donated by Dr A. N. Barclay) did not reduce terminal sprouting significantly when compared with non-immune serum-treated controls. We conclude that the expression of neural cell adhesion molecule in inactivated muscles may be at least partially responsible for the effectiveness of the terminal sprouting response. © 1990.