P75 nerve growth factor receptors modulate development of GnRH neurons and olfactory ensheating cells

Abstract

Temporal and spatial localization of nerve growth factor receptor (p75NGFR) in the developing olfactory system and gonadotropin-releasing hormone-1 (GnRH) system was characterized and its role analyzed using p75NGFR null mice and nasal explants. Prenatally, p75NGFR was expressed by GnRH neurons and olfactory ensheathing cells (OECs). In p75NGFR null mice, no change in the number of GnRH cells was detected as compared to wild-type. However, in null mice, a shift in the distribution of GnRH neurons was found, with a small population of GnRH cells migrating further caudally toward the median eminence. Additionally, a reduction of both GAD67 positive olfactory axons and GFAP positive OEC fibers occurred. Acute administration of a p75NGFR blocker to GnRH cells maintained in vitro increased migration rate, consistent with the change in distribution detected in p75NGFR null mice. Chronic inhibition of p75NGFR caused an attenuation of olfactory axon fasciculation and a decrease in OEC density, again mimicking the changes detected in null mice. However, a reduction in GnRH cell number was found after chronic treatment that not observed in KO animals suggesting indirect changes occur during chronic treatment in vitro and/or a compensatory mechanism occurs in vivo that prevents loss of GnRH neurons in the absence of p75NGFR.

Selective Cre‐mediated gene deletion identifies connexin 43 as the main connexin channel supporting olfactory ensheathing cell networks

“…Knowledge about roles of OECs in vivo has emerged from noninducible knock‐down and null mice (Au et al, ; Ingram, Khankan, & Phelps, ; Murthy et al, ; Raucci, Tiong, & Wray, ). Selective genetic manipulation of OECs has been achieved using viral vectors in enriched OEC preparations to be used in transplants (Cao et al, ; Ruitenberg et al, ).…”

GnRH, anosmia and hypogonadotropic hypogonadism – Where are we?

“…embryonic lineage of the initial progenitor cells as well as whether different GnRH lineage derived-subpopulations play distinct physiological roles. However, it is broadly accepted in mammals, at least after specification, that 1) GnRH-1 neurons migrate from the nasal area to the central nervous system, 2) GnRH-1 neuronal migration is axophilic in that they use axons of the terminal nerve/olfactory pathways to reach their final position [120; 125], and 3) GnRH-1 neurons migrate with other migratory neurons [126] and olfactory ensheathing cells [127; 128]. KS patients have mutations that alter 1 or more of these events.…”

Rostro‐caudal maturation of glial cells in the accessory olfactory system during development: involvement in outgrowth of GnRH neurites

“…Nasal explant culture is an ideal model to study GnRH neurones migration and also OEC migration from the olfactory placode to the outside of the explant (Forni et al . , Geller et al ., ; Raucci et al ., ). The depletion of proliferative [GFAP+] cells was induced by adding antiviral drug ganciclovir (GCV) in the culture medium, and the effect was assessed using immunofluorescence.…”

“…Further work on Sox10 Knockout mice embryos has shown that a reduction in the number of OEC progenitors (pOEC) which are BLBP+ (brain lipid binding protein) in the NS causes a default of GnRH neurones migration but does not impact vomeronasal/olfactory axon formation (Barraud et al ., ; Pingault et al ., ). In p75 NTR Knockout mice, deleting p75 NTR expression in GnRH neurones and OEC has been shown to modulate GFAP+ OEC maturation, GnRH cell survival and neuronal migration (Raucci et al ., ). Overall, these data suggest that disruption of OEC differentiation/maturation could cause a default of GnRH neurones ontogenesis.…”