Neuropeptide Y and peptide YY have distinct roles in adult mouse olfactory neurogenesis.

Neuropeptide Y (NPY) and peptide YY (PYY) are differentially expressed throughout the olfactory neuroepithelium (ON), with NPY expression present in sustentacular cells, olfactory ensheathing cells, and olfactory receptor neurons and PYY expressed only in sustentacular cells. Examination of the anatomical morphology of the ON in NPY knockout (NPY⁻/⁻) and PYY knockout (PYY⁻/⁻) mice shows that there are significantly more neurons in PYY⁻/⁻ mice and significantly fewer neurons in NPY⁻/⁻ mice. Interestingly, the mature neurons of NPY⁻/⁻ mice were undergoing apoptosis. The transcription factor Mash1, which is critical in the production of olfactory precursors, is also differentially expressed in NPY⁻/⁻ and PYY⁻/⁻ ON. It is upregulated in the neurons of NPY⁻/⁻ mice and unchanged in PYY⁻/⁻ mice. Furthermore, significantly fewer olfactory neurospheres are present in cultures prepared from PYY⁻/⁻ mice in the first 2 weeks compared with NPY⁻/⁻ and wild-type mice. Together these results suggest that, during olfactory neurogenesis, NPY acts as a trophic factor for the maturation and survival of olfactory receptor neurons, whereas PYY has an important role in the regulation of olfactory neuron differentiation.