The p75 neurotrophin receptor is expressed in brain regions mastering reproduction but not in kisspeptin or <scp>GnRH</scp> neurons

Neurotrophins (BDNF, NGF, NT3, and NT4/5) acting through different receptors are able to impact numerous functions, including cell fate and morphological plasticity, an asset for the maturation and differentiation of cells from neurogenic niches. They bind to the neurotrophin receptor p75 (p75), which could either heterodimerize with Trk receptors or act on its own to relay the varied physiological functions of neurotrophins. Published data suggest a preponderant role of p75 for NGF stimulation of GnRH neurons in vitro. We therefore focused on this receptor and its relationships with neuronal populations involved in the central control of reproduction. Here we investigated the distribution and phenotype of p75 cells in the hypothalamus of ovariectomized estrogen-replaced mice using several combinations of immunohistochemical labeling. We found that p75 is expressed mainly in neurons of the organum vasculosum of the lamina terminalis (OVLT)-medial septum continuum and in the arcuate nucleus (ARC). In this latter region, p75 was also seen in tanycytic cells lining the third ventricle. Co-distribution of p75 with TrkA was only seen in the OVLT, an area in which p75 is present in 16% of nitric oxide synthase-expressing neurons. In the ARC, 33% of p75 neurons were colocalized with tyrosine hydroxylase, an enzyme essential for catecholamine production. Anatomical distribution and co-expression with neurotransmitters involved in reproduction control, together with data suggesting that β-NGF induced ovulation in camelidae, prompted us to perform immunohistochemical double labeling against p75 and kisspeptin or GnRH, two neuropeptides essential for the central control of ovulation. However, no colocalization of p75 with kisspeptin or GnRH neurons was seen. These results suggest that neurotrophins, acting via the p75 receptor, do not directly modulate GnRH or Kp neurons. On the other hand, they may influence dopamine and nitric oxide production, and possibly induce remodeling of tanycytic endfeet, ultimately impacting indirectly the central regulation of reproduction in mice.