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Neuropeptide Y functions as a neuroproliferative factor

Nature volume 410, pages 940–944 (2001)Cite this article

Abstract

Neuropeptide Y (NPY) has a number of functions in mammalian physiology1,2,3,4,5,6. Here we identify a role for NPY in promoting proliferation of postnatal neuronal precursor cells. NPY is synthesized in the postnatal olfactory epithelium by sustentacular cells, previously proposed to function only in structural support7. Mice with a targeted deletion of NPY8 contain half as many dividing olfactory neuronal precursor cells as do controls. Furthermore, NPY-deficient mice develop significantly fewer olfactory neurons by adulthood. NPY acts on multipotent neuronal precursor or basal cells to activate rapidly and transiently the extracellular signal-regulated kinase (ERK)1/2 subgroup of mitogen-activated protein kinases. The NPY Y1 receptor subtype appears to mediate this effect. The ability of NPY to induce neuronal precursor proliferation is mediated by protein kinase C (PKC), indicating an upstream PKC-dependent activation of ERK1/2. These results indicate that NPY may regulate neuronal precursor proliferation in the adult mammal.

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Figure 1: NPY expression in the olfactory epithelium.
Figure 2: NPY-deficient mice8 show decreased precursor proliferation and decreased neuronal number.
Figure 3: NPY stimulates neuroproliferation.
Figure 4: Y1 receptors mediate the NPY response.
Figure 5: NPY induces neuroproliferation through ERK1/2 phosphorylation and activation.

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Acknowledgements

We thank A. Hanlon and M. Bell for technical support, and R. Mains and C. Hansel for comments on the manuscript. The NPY-deficient mice were a gift from R. D. Palmiter at the University of Washington; mouse genotyping was performed by G. Miura in the laboratory of R. D. Palmiter.

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Authors and Affiliations

  1. Departments of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    D. E. Hansel, B. A. Eipper & G. V. Ronnett

  2. Departments of Neurology, The Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    G. V. Ronnett

  3. Department of Physiology, University of Connecticut Health Science Center, Farmington, 05405, Connecticut, USA

    B. A. Eipper

Authors
  1. D. E. Hansel
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  3. G. V. Ronnett
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Correspondence to G. V. Ronnett.

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Hansel, D., Eipper, B. & Ronnett, G. Neuropeptide Y functions as a neuroproliferative factor. Nature 410, 940–944 (2001). https://doi.org/10.1038/35073601

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