Prenatal development of hypothalamic neuropeptide systems in the nonhuman primate

In the rodent, arcuate nucleus of the hypothalamus (ARH)-derived neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons have efferent projections throughout the hypothalamus that do not fully mature until the second and third postnatal weeks. Since this process is likely completed by birth in primates we characterized the ontogeny of NPY and melanocortin systems in the fetal Japanese macaque during the late second (G100), early third (G130) and late third trimesters (G170). NPY mRNA was expressed in the ARH, paraventricular nucleus (PVH), and dorsomedial nucleus of the hypothalamus (DMH) as early as G100. ARH-derived NPY projections to the PVH were initiated at G100 but were limited and variable; however, there was a modest increase in density and number by G130. ARH-NPY/agouti-related peptide (AgRP) fiber projections to efferent target sites were completely developed by G170, but the density continued to increase in the postnatal period. In contrast to NPY/AgRP projections, αMSH fibers were minimal at G100 and G130 but were moderate at G170. This study also revealed several significant species differences between rodent and the nonhuman primate (NHP). There were few NPY/catecholamine projections to the PVH and ARH prior to birth, while projections were increased in the adult. A substantial proportion of the catecholamine fibers did not coexpress NPY. In addition, cocaine and amphetamine-related transcript (CART) and alpha-melanocyte stimulating hormone (αMSH) were not colocalized in fibers or cell bodies. As a consequence of the prenatal development of these neuropeptide systems in the NHP, the maternal environment may critically influence these circuits. Additionally, because differences exist in the neuroanatomy of NPY and melanocortin circuitry the regulation of these systems may be different in primates than in rodents.