Are neurons of the arcuate nucleus necessary for pathfinding by GnRH fibers arising from third ventricular grafts?

Abstract

The hypogonadal (hpg) mouse lacks GnRH due to a severe truncation of the gene by which it is encoded. This results in an infertile animal with an infantile reproductive system. When fetal or 1-day postnatal septal/preoptic area of a normal mouse is grafted into the third ventricle of an hpg mouse, GnRH-containing fibers grow out of the grafts and innervate the host median eminence (ME), a normal target of these fibers. GnRH axons exiting the graft course follow a very stereotyped pathway through host tissue. They are observed passing through the ependymal wall of the ventricle directly into the ME or arching through the host arcuate nucleus to terminate in the host ME. Given the fixed pattern of outgrowth, we wanted to determine if the neurons of the arcuate nucleus, which lie between the graft and its target, are exerting an influence on the growth and direction of these fibers. The excitotoxin monosodium glutamate (MSG) has been shown to destroy the vast majority of arcuate neurons when administered neonatally. Mutant host animals treated with MSG received fetal grafts of normal septal/preoptic area. Brains were examined for GnRH fiber outgrowth 30 days later to assess early outgrowth which preferentially uses the arcuate route. We report here that the pattern of outgrowth is virtually identical to that observed in saline-injected, grafted animals. There is also no difference in the success rate of grafts placed in control vs MSG-treated hosts nor in the stimulation of testicular growth. The results of this experiment imply that axonal outgrowth to the ME does not rely on arcuate neurons for guidance information or trophic substances. These functions may be subserved by glia, tanycytes/ependyma, or the target.