Grayson B E, Allen S E, Billes S K, Williams S M, Smith M S, Grove K L
Division of Neuroscience, Oregon Health and Science University, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Neuroscience. 2006 Dec 28;143(4):975-86. doi: 10.1016/j.neuroscience.2006.08.055. Epub 2006 Oct 9.
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, alphaMSH 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 (alphaMSH) 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.
在啮齿动物中，下丘脑弓状核（ARH）衍生的神经肽Y（NPY）和阿黑皮素原（POMC）神经元具有贯穿下丘脑的传出投射，这些投射直到出生后第二和第三周才完全成熟。由于这个过程在灵长类动物中可能在出生时就已完成，我们对胎龄第二期末（G100）、第三期初（G130）和第三期末（G170）的日本猕猴胎儿中NPY和黑皮质素系统的个体发生进行了表征。早在G100时，NPY mRNA就在ARH、室旁核（PVH）和下丘脑背内侧核（DMH）中表达。源自ARH的NPY向PVH的投射在G100时开始，但有限且多变；然而，到G130时，密度和数量有适度增加。到G170时，ARH-NPY/刺鼠相关肽（AgRP）纤维向传出靶位点的投射已完全发育，但在出生后密度仍持续增加。与NPY/AgRP投射相反，α-MSH纤维在G100和G130时极少，但在G170时适中。这项研究还揭示了啮齿动物和非人灵长类动物（NHP）之间的几个显著物种差异。出生前，向PVH和ARH的NPY/儿茶酚胺投射很少，而在成年动物中投射增加。相当一部分儿茶酚胺纤维不共表达NPY。此外，可卡因和苯丙胺相关转录物（CART）与α-黑素细胞刺激素（α-MSH）不在纤维或细胞体中共定位。由于这些神经肽系统在NHP中的产前发育，母体环境可能对这些回路产生关键影响。此外，由于NPY和黑皮质素回路的神经解剖学存在差异，这些系统在灵长类动物中的调节可能与啮齿动物不同。
