Research ReportThe brainstem preproglucagon system in a non-human primate (Macaca mulatta)

The nucleus of the solitary tract (NTS) contains a small population of neurons expressing preproglucagon. In these neurons preproglucagon is processed to the glucagon-like-peptides 1 and 2 (GLP-1 and GLP-2) and oxyntomodulin. Whereas the neuroanatomy of these neurons is well characterized in rodents the location and projection of preproglucagon neurons have never been described in primates. The purpose of the present study was to characterize the location of preproglucagon neurons and their projections in the non-human primate using radioactive in situ hybridization and immunohistochemistry. In situ hybridization revealed preproglucagon mRNA expressing neurons in the caudal nucleus of the solitary tract extending laterally through the intermediate reticular nucleus into the A1 area. Using an antibody raised against rat GLP-2, GLP-2-immunoreactive (− ir) cell bodies were found in the same areas as the preproglucagon mRNA. Only very few GLP-2-ir nerve fibers were observed in the caudal brainstem and mostly in the same areas as the GLP-2-ir cell bodies. The most prominent GLP-2-ir terminal fields were detected in the hypothalamus and rostrally in the bed nucleus of the stria terminalis complex. In the hypothalamus, GLP-2-ir fibers arborized extensively in the paraventricular nucleus of the hypothalamus (PVN), the dorsomedial hypothalamic nucleus (DMH) and the arcuate nucleus (Arc), the latter containing the densest fiber-plexus. The findings indicate that the brainstem preproglucagon neuronal system is highly conserved between rat and non-human primate with the exception of a much denser innervation of the mediobasal hypothalamus in the primate brain.

Research highlights► First report of preproglucagon expression and GLP-ir in the primate brain. ► Most comprehensive study of NTS-hypothalamus projections in the primate. ► Data indicate important species differences in brainstem-hypothalamus projections.