Neuropeptide Y is important for basal and seizure-induced precursor cell proliferation in the hippocampus

Neurobiol Dis. 2007 Apr;26(1):174-88. doi: 10.1016/j.nbd.2006.12.014. Epub 2006 Dec 30.


We have shown that neuropeptide Y (NPY) regulates neurogenesis in the normal dentate gyrus (DG) via Y(1) receptors (Howell, O.W., Scharfman, H.E., Herzog, H., Sundstrom, L.E., Beck-Sickinger, A. and Gray, W.P. (2003) Neuropeptide Y is neuroproliferative for post-natal hippocampal precursor cells. J Neurochem, 86, 646-659; Howell, O.W., Doyle, K., Goodman, J.H., Scharfman, H.E., Herzog, H., Pringle, A., Beck-Sickinger, A.G. and Gray, W.P. (2005) Neuropeptide Y stimulates neuronal precursor proliferation in the post-natal and adult dentate gyrus. J Neurochem, 93, 560-570). This regulation may be relevant to epilepsy, because seizures increase both NPY expression and precursor cell proliferation in the DG. Therefore, the effects of NPY on DG precursors were evaluated in normal conditions and after status epilepticus. In addition, potentially distinct NPY-responsive precursors were identified, and an analysis performed not only of the DG, but also the caudal subventricular zone (cSVZ) and subcallosal zone (SCZ) where seizures modulate glial precursors. We show a proliferative effect of NPY on multipotent nestin cells expressing the stem cell marker Lewis-X from both the DG and the cSVZ/SCZ in vitro. We confirm an effect on proliferation in the cSVZ/SCZ of Y(1) receptor(-/-) mice and demonstrate a significant reduction in basal and seizure-induced proliferation in the DG of NPY(-/-) mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites
  • Bromodeoxyuridine
  • Cell Count
  • Cell Proliferation
  • Cells, Cultured
  • Dentate Gyrus / cytology
  • Hippocampus / cytology*
  • Hippocampus / pathology
  • Hippocampus / physiology*
  • Immunohistochemistry
  • Intermediate Filament Proteins / metabolism
  • Intermediate Filament Proteins / physiology
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology
  • Nestin
  • Neurons / physiology*
  • Neuropeptide Y / genetics
  • Neuropeptide Y / physiology*
  • Rats
  • Rats, Wistar
  • Seizures / chemically induced
  • Seizures / pathology*
  • Stem Cells / physiology*
  • Tubulin / metabolism


  • Antimetabolites
  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nes protein, rat
  • Nestin
  • Neuropeptide Y
  • Tubulin
  • Bromodeoxyuridine