NPY and its involvement in axon guidance, neurogenesis, and feeding

Objectives The role of neuropeptides in nervous system function is still in many cases undefined. In the present study we examined a possible role of the 36–amino acid neuropeptide Y (NPY) with regard to three functions: axon guidance and attraction/repulsion, adult neurogenesis, and control of food intake. Methods Growth cones from embryonic dorsal root ganglion neurons were studied in culture during asymmetrical gradient application of NPY. Growth cones were monitored over a 60-min period, and final turning angle and growth rate were recorded. In the second part the NPY Y1 and Y2 receptors were studied in the subventricular zone, the rostral migratory stream, and the olfactory bulb in normal mice and mice with genetically deleted NPY Y1 or Y2 receptors. In the third part an anorectic mouse was analyzed with immunohistochemistry. Results 1) NPY elicited an attractive turning response and an increase in growth rate, effects exerted via the NPY Y1 receptor. 2) The NPY Y1 receptor was expressed in neuroblasts in the anterior rostral migratory stream. Mice deficient in the Y1 or Y2 receptor had fewer proliferating precursor cells and neuroblasts in the subventricular zone and rostral migratory stream and fewer neurons in the olfactory bulb expressing calbindin, calretinin or tyrosine hydroxylase. 3) In the anorectic mouse markers for microglia were strongly upregulated in the arcuate nucleus and in projection areas of the NPY/agouti gene-related protein arcuate system. Conclusion NPY participates in several mechanisms involved in the development of the nervous system and is of importance in the control of food intake.