Postnatal development of the hypothalamic neuropeptide Y system

Abstract

In the adult rat, arcuate-neuropeptide Y/agouti-related protein neurons have efferent projections throughout the hypothalamus and provide a potent orexigenic stimulus. At birth neuropeptide Y fibers are also present throughout the hypothalamus; however, the source of these fibers has been unknown. The present studies determined the postnatal ontogeny of arcuate-neuropeptide Y fibers into the paraventricular nucleus and dorsomedial hypothalamic nucleus, as well as the ontogeny of neuropeptide Y1 receptor expression within these areas. Agouti-related protein messenger RNA and protein expression was present exclusively in cell bodies in the arcuate throughout postnatal development, starting at P2, and was colocalized in the vast majority of arcuate-neuropeptide Y neurons. This exclusive colocalization of agouti-related protein with arcuate-neuropeptide Y neurons makes it an excellent marker for these neurons and their projections. Even though single-label neuropeptide Y fibers were abundant in the dorsomedial hypothalamic nucleus and paraventricular nucleus as early as P2, arcuate-neuropeptide Y/agouti-related protein fibers did not significantly innervate these areas until P5-6 and P10-11, respectively. In contrast, a portion of the neuropeptide Y fibers within the paraventricular nucleus as early as P2 originated from the brainstem, as indicated by their colocalization with dopamine β hydroxylase. It remains to be determined if local sources of neuropeptide Y-expressing cells within the dorsomedial hypothalamic nucleus and paraventricular nucleus also contribute to the neuropeptide Y-immunoreactive fibers within these regions prior to the development of arcuate-neuropeptide Y/agouti-related protein projections. In addition to the dramatic change in arcuate-neuropeptide Y/agouti-related protein projections, there is also a striking change in Y1 protein expression in the hypothalamus during the first two postnatal weeks. Taken together these data suggest that the early postnatal period, during which there is a dynamic change in the hypothalamic neuropeptide Y system, may constitute a critical period in the development of this important feeding circuit.