ACETYLCHOLINESTERASE ANTIBODY TREATMENT RESULTS IN NEURITE DETACHMENTAND REDUCED OUTGROWTH FROM CULTURED NEURONS - FURTHER EVIDENCE FOR A CELL ADHESIVE ROLE FOR NEURONAL ACETYLCHOLINESTERASE

Data from our laboratory and others demonstrate that acetylcholinester ase (AChE)is expressed transiently by neurons during periods of neurit e outgrowth preceding synaptogenesis, suggesting an extrasynaptic func tion for this molecule. These findings, along with reports that AChE s hares amino acid sequence homology and structural similarities with kn own cell adhesion molecules, have led to the theory that, during devel opment, AChE may exert a morphogenic effect through cell adhesion. To further test this hypothesis, we have examined the effects of an AChE monoclonal antibody (MAB304) on neurite outgrowth in primary cultures of rat dorsal root ganglion (DRG) neurons. Short-term, high-concentrat ion antibody treatment produced a rapid detachment of established DRG neurites, which was followed by regrowth upon removal of the antibody from the culture medium. This effect appeared to be site-specific, bec ause other AChE antibodies that were able to detect AChE immunocytoche mically failed to produce this disadhesion. Long-term, low-concentrati on antibody exposure produced a 50% reduction in total area of outgrow th, in which neurites were more densely packed and interlaced compared with the neurites in control cultures. These results extend our previ ous observations on the outgrowth perturbing effects of AChE inhibitor treatment and provide further evidence that AChE may support neurite outgrowth through a cell adhesive role. (C) 1998 Wiley-Liss, Inc.