Characterization of neuropeptide Y Y2 and Y5 receptor expression in the mouse hypothalamus

Neuropeptide Y (NPY) neurons abundantly innervate the hypothalamus, where NPY is involved in the regulation of a broad range of homeostatic functions. In the present work we studied NPY Y2 and Y5 receptor (R) gene expression in the mouse hypothalamus by using immunohistochemical detection of β-galactosidase (β-gal), a gene reporter molecule for Y2R and Y5R in Y2R-knockout (KO) and Y5R-KO mice, respectively. With this approach, cells normally expressing Y2R or Y5R are immunopositive for β-gal. In the hypothalamus of the Y2R-KO mouse, β-gal immunoreactivity (-ir) was found in numerous neurons of the medial preoptic nucleus as well as in the lateral anterior, periventricular, dorsomedial, tuberal, perifornical, and arcuate nuclei. Most of the dopaminergic neurons in the A13 dorsal hypothalamic group were β-gal positive, whereas other hypothalamic dopaminergic neurons rarely displayed β-gal-ir. In the arcuate nucleus, most of the β-gal-positive neurons expressed NPY, but colocalizations with β-endorphin were also found; in the tuberal and perifornical nuclei, many β-gal-positive neurons contained nitric oxide synthase. β-Gal-ir was also found in other forebrain regions of the Y2R-KO mouse, including the amygdala, thalamic nuclei, hippocampal CA3 area, and cortex. In the hypothalamus of the Y5R-KO mouse, β-gal-positive neurons were found mainly in the arcuate nucleus and contained β-endorphin. The present data show that Y2R and Y5R are expressed in distinct groups of hypothalamic neurons. High levels of Y2R expression in the preoptic nuclei suggest an involvement of Y2R in the regulation of reproductive behavior, whereas Y2R expression in the arcuate, dorsomedial, and perifornical nuclei may be relevant to feeding and body weight control. The finding that A13 dopaminergic neurons express Y2R suggests a new mechanism putatively involved in the central control of feeding, in which NPY can modulate dopamine secretion. The distribution of Y5R expression supports earlier evidence for involvement of this receptor in control of feeding and body weight via NPY's action on proopiomelanocortin-expressing neurons. J. Comp. Neurol. 470:256–265, 2004. © 2004 Wiley-Liss, Inc.