Interconnection between orexigenic neuropeptide Y- and anorexigenic α-melanocyte stimulating hormone-synthesizing neuronal systems of the human hypothalamus

Peripheral feeding-related hormones such as leptin, insulin, and ghrelin exert their main central effects through neuropeptide Y- (NPY) synthesizing and α-melanocyte-stimulating hormone- (α-MSH) synthesizing neurons of the hypothalamic arcuate nucleus. In rodents, recent reports have described an asymmetric signaling between these neuron populations by showing that while NPY influences α-MSH-synthesizing neurons, the melanocortin-receptor agonist Melanotan II (MTII) does not modulate the electrophysiological properties of NPY neurons. The functional neuroanatomy of the relationship between these cell populations is unknown in humans. The aim of the current study was to analyze the putative relationship of the orexigenic NPY and anorexigenic α-MSH systems in the infundibular nucleus of the human hypothalamus, the analogue of the rodent arcuate nucleus. Double-labeling fluorescent immunocytochemistry for NPY and α-MSH was performed on postmortem sections of the human hypothalamus. The sections were analyzed by confocal laser microscopy. Both NPY- and α-MSH-immunoreactive (IR) neurons were embedded in dense, intermingling networks of NPY- and α-MSH-IR axons in the human infundibular nucleus. NPY-IR varicosities were observed in juxtaposition to all α-MSH-IR neurons. The mean number of NPY-IR axon varicosities on the surface of an α-MSH-IR neuron was approximately six. The majority of NPY-IR neurons were also contacted by α-MSH-IR varicosities, although, the number of such contacts was lower (two α-MSH-IR varicosities per NPY neuron). In summary, the present data demonstrate that these two antagonistic, feeding-related neuronal systems are interconnected in the infundibular nucleus, and the neuronal wiring possesses an asymmetric character in the human hypothalamus.