Long-term effects of nerve growth factor and neural transplants on behavior of rats with medial septal lesions.

The present experiment investigated the interaction between exogenous nerve growth factor (NGF) and intrahippocampal septal grafts on the behavior of rats after a medial septum lesion. Young female rats received a bilateral injection of a fetal septal cell suspension into the dorsal hippocampus either immediately (immediate grafts) or 8 days after the lesion (delayed grafts). For delayed grafts, a higher concentration of endogenous neurotrophic factors can be assumed to be present in the deafferentated host tissue at the time of transplantation. One group of rats with lesions received NGF with the immediate grafts, another group received NGF alone. A sham-operated group and 3 groups with lesions (and given either immediate or delayed intrahippocampal saline injections, or no other treatment) constituted controls. The animals were tested for spontaneous alternation and for performance in a radial 8-arm maze, 1, 5 and 9 months postoperatively. Medial septal lesions reduced spontaneous alternation but, 9 months after surgery, recovery was observed in both lesion-control rats and in rats with delayed grafts (but not with immediate grafts). In the radial maze task, lesions produced a persistent impairment, although both immediate and delayed grafts reduced this deficit several months after surgery (more markedly and rapidly in the case of delayed grafts). NGF, however, increased the maze learning deficit especially 5 months postoperatively. These latter results are in contrast to findings of earlier studies showing transient beneficial effects of NGF administration. It is suggested that the effects of NGF in the present study might be due to an enhanced sprouting of sympathetic fibers into the hippocampal formation.