Regulation of olfactory neurogenesis by amidated neuropeptides

The existence of stem cells in the CNS raises issues concerning the ability of nervous tissues to regenerate in the adult mammal and provides new perspectives on the treatment of degenerative disease and traumatic injury of the nervous system. These cells have a relatively limited range of locations within the nervous system and include cells of the rostral migratory stream, hippocampus, retina, and olfactory epithelium. The olfactory epithelium has been studied as a model of adult neuronal regeneration, with neuronal precursor/basal cells serving as the olfactory "stem cells." The identification of factors that promote neuronal proliferation or regeneration within the olfactory epithelium can provide clues to the process of adult mammalian nervous system repair and treatment. Multiple factors have been examined that appear to influence the proliferation and subsequent maturation of basal cells. These factors include nerve growth factor, fibroblast growth factor-2, epidermal growth factor, and insulin/insulin-like growth factor-1. Recently, two amidated neuropeptides, neuropeptide Y (NPY) and pituitary adenylate cyclase-activating polypeptide (PACAP38), identified in the olfactory epithelium have been shown to promote dramatically neuronal proliferation. The effects of NPY and PACAP suggest that amidated neuropeptides may serve a broad developmental and regenerative role in the mammalian olfactory epithelium.