Neuropeptide Y is important for basal and seizure-induced precursor cell proliferation in the hippocampus.
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.
Howell
Owain W
OW
Division of Clinical Neurosciences, University of Southampton, Room LD70, D Level, South Academic Block, Southampton General Hospital, Southampton SO16 6YD, UK.
Silva
Sharmalene
S
Scharfman
Helen E
HE
Sosunov
Alexander A
AA
Zaben
Malik
M
Shtaya
Anan
A
Shatya
Anan
A
McKhann
Guy
G
Herzog
Herbert
H
Laskowski
Alexandra
A
Gray
William P
WP
D000818:Animals; D000963:Antimetabolites; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology; D006624:Hippocampus / Q000166:cytology* / Q000473:pathology / Q000502:physiology*; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology; D064231:Nestin; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*; D013234:Stem Cells / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism
D000963:Antimetabolites; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; C577486:Nes protein, rat; D064231:Nestin; D009478:Neuropeptide Y; D014404:Tubulin; D001973:Bromodeoxyuridine