New perspectives for anatomical and molecular studies of kisspeptin neurons in the aging human brain

The human infundibular nucleus (corresponding to the rodent arcuate nucleus) serves as an important integration center for neuronal signals and hormones released by peripheral endocrine organs. Kisspeptin (KP) producing neurons of this anatomical site many of which also synthesize neurokinin B (NKB) are critically involved in sex hormone signaling to gonadotropin-releasing homone (GnRH) neurons. In recent years, the basic topography, morphology, neuropeptide content and connectivity of human KP neurons have been investigated with in situ hybridization and immunohistochemistry on post mortem tissues. These studies revealed that human KP neurons differ neurochemically from their rodent counterparts and show robust aging-related plasticity. Earlier immunohistochemical experiments also provided evidence for temporal changes in the hypothalamus of aging men whose NKB and KP neurons undergo hypertrophy, increase in number, exhibit increased neuropeptide mRNA expression and immunoreactivity and give rise to higher numbers of immunoreactive fibers and afferent contacts onto GnRH neurons. Increasing percentages of KP-expressing NKB perikarya, NKB axons and NKB inputs to GnRH neurons raise the intriguing possibility that a significant subset of NKB neurons begins to co-synthesize KP as aging proceeds. Although use of post mortem tissues is technically challenging, recently-available single-cell anatomical and molecular approaches discussed in this review article provide promising new tools to investigate the aging-related anatomical and functional plasticity of the human KP neuronal system..