CHOLINERGIC INNERVATION OF FETAL NEOCORTICAL TRANSPLANTS IS INCREASEDAFTER NEUTRALIZATION OF MYELIN-ASSOCIATED NEURITE GROWTH-INHIBITORS

Fetal neocortical transplants placed into adult neocortical sensorimot or aspiration lesions are known to receive afferent input from the adu lt host rat brain. As this input is less dense than normal, the presen t study was designed to investigate whether neutralization of myelin-a ssociated neurite growth inhibitors NI-35/250 might promote host deriv ed cholinergic innervation of fetal neocortical transplants. Adult rat s received unilateral. sensorimotor cortical aspiration lesions, and b lock grafts from embryonic day 14-15 neocortical tissue were placed im mediately into the lesion cavities. Mouse hybridoma cells secreting ei ther the monoclonal antibody IN-1, which blocks neurite growth inhibit ors NI-35/250, or a control antibody or medium without cells were appl ied in millipore filter capsules directly over the fetal graft tissue, The brains were processed 12 weeks later for the visualization of ace tylcholinesterase-positive, presumptive cholinergic fibers. We found a n enhancement in the cholinergic innervation of fetal grafts in the re cipients treated with the antibody IN-1 both in terms of fibers growin g into the graft and of density within the center of the grafts. These results indicate that myelin-associated neurite growth inhibitors are involved in the development of host-transplant connectivity in the ad ult brain, (C) 1998 Academic Press.