Hypothalamic circuitry of neuropeptide Y regulation of neuroendocrine function and food intake via the Y5 receptor subtype

Neuropepticle Y (NPY) displays diverse modes of action in the CNS including the modulation of feeding behavior, gonaclotropin releasing hormone releas e, and stress responses. Many of the above physiological actions have been at least partially attributed to actions of NPY on the NPY Y5 receptor subt ype. We utilized an antibody directed against the NPY Y5 receptor to charac terize the distribution of this receptor in the rat brain. Using Western bl ot analysis, this antibody recognized a single major band at approximately 57 kD. To further verify the specificity of the antibody, animals were trea ted for 5 days with antisense oligonucleoticles for the Y5 receptor. The an tisense treatment significantly reduced food intake and body weight. Furthe rmore, the Y5 antibody detected a significant decrease in Y5 receptor prote in. Y5-like immunoreactivity (-ir) was observed throughout the hypothalamus , thalamus, hippocampus and cortex. Double-label immunofluorescence demonst rated that Y5-ir was colocalized with the following neuronal phenotypes in the hypothalamus, gonadotropin-releasing hormone, neurophysins, corticotrop in-releasing hormone, and gamma -amino butyric acid. In addition, functiona l interactions were demonstrated by the presence of close appositions of NP Y fibers with Y5-ir expressing cells. The wide distribution of the Y5 recep tor-ir, as well as the colocalization within specific neuronal populations, agrees with the distribution of the Y5 receptor mRNA and the known physiol ogical roles of the NPY/Y5 system. The role of the NPY/ Y5 receptor system as a mediator between signals of peripheral energy availability and reprodu ctive neuroendocrine function is discussed. Copyright (C) 2001 S. Karger AG , Basel.