NEUROTROPISM OF NERVE GROWTH-FACTOR FOR ADULT-RAT SEPTAL CHOLINERGIC AXONS INVIVO

Nerve growth factor (NGF) can induce sprouting of axotomized adult rat medial septum cholinergic neurons and promote their regeneration into septohippocampal nerve grafts and hippocampal formation. This study investigated the potential neurotropic (chemotactic/attracting) action of NGF in the adult rat cholinergic septohippocampal regeneration model. (i) Some animals received sciatic nerve grafts between the disconnected septum and hippocampal formations on each side. A 4-week infusion with NGF into the rostral portion of the lateral ventricle induced sprouting of cholinergic fibers in the dorsolateral septum with a gradient toward the lateral ventricle. However, the number of cholinergic axons entering the nerve bridge was only one-third that observed in vehicle-infused animals, suggesting that NGF had diverted many of the regrowing axons away from the nerve toward the ventricle. (ii) In animals implanted with nerves for 2 weeks and concurrently infused with NGF into the fornix, proximal to the lesion and grafts, cholinergic sprouting occurred in the mediodorsal septum, i.e., was oriented toward the infused fornix. Essentially no fibers had entered the nerve bridge, suggesting that all regrowing fibers had remained near the NGF source. (iii) When animals with a unilateral fimbria-fornix transection (but no nerve graft) were infused with NGF into the lateral ventricle on the opposite side, cholinergic sprouting was oriented toward the midline of the septum. (iv) Infusion of low doses of NGF directly into the (lesioned) septum induced a sprouting response localized around the infusion site. (v) No sprouting occurred when intraventricular NGF infusion was applied to normal (nonlesioned) animals. These results show that the location of an NGF source can control the orientation of the outgrowing cholinergic axons, and indicate that NGF has a neurotropic action in the adult animal in vivo, as it has been shown to have for developing neurons both in vitro and in vivo. © 1993 Academic Press, Inc.