Substance P is a promoter of adult neural progenitor cell proliferation under normal and ischemic conditions.
OBJECTIVE
Neurogenesis continues throughout the life of mammals in the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus (DG) of the hippocampus. The authors tested the potential of the neuropeptide substance P (SP) acting via the neurokinin-1 receptor (NK1R) in promoting the proliferation of adult rat neural progenitor cells (NPCs).


METHODS
Focal ischemia was induced in spontaneously hypertensive rats by transient middle cerebral artery occlusion. Substance P and the NK1R antagonist L-703,606 were infused into the lateral ventricles of rats by using Alzet osmotic minipumps. Progenitor cell proliferation was evaluated with immunostaining for bromodeoxyuridine (BrdU) and immature neural marker doublecortin (DCX). Neurospheres were cultured from the SVZ of adult rats.


RESULTS
Under in vitro conditions, SP (0.01-10 micromol/L) increased the proliferation of cultured NPCs, with a peak increase of 52 +/- 7% at 0.1 micromol/L. Substance P (0.1 micromol/L) continuously increased NPC proliferation from 6 hours to 5 days, which was prevented by L-703,606 (by 69-98%). The cultured NPCs expressed both SP and NK1R proteins, indicating that these effects are receptor specific. Continuous infusion of SP (1 micromol/L) into the lateral ventricles for 5 days significantly increased the number of proliferating NPCs (cells positive for both BrdU and DCX) in both the SVZ (by 173 +/- 24%, p < 0.05) and DG (by 82 +/- 12%, p < 0.05) in adult rats; however, infusion of L-703,606 (10 micromol/L) significantly prevented the postischemic induction of NPC proliferation in both the SVZ (by 84 +/- 6%, p < 0.05) and DG (by 63 +/- 7%, p < 0.05).


CONCLUSIONS
Data in these studies indicated that SP plays a role in normal and ischemia-induced neurogenesis in the adult brain and thus could help central nervous system plasticity following injury.
Park
Seung-Won
SW
Department of Neurological Surgery, University of Wisconsin-Madison, Wisconsin 53792, USA.
Yan
Yi-Ping
YP
Satriotomo
Irawan
I
Vemuganti
Raghu
R
Dempsey
Robert J
RJ
D053687:Adult Stem Cells / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects*; D000089662:Doublecortin Protein; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013373:Substance P / Q000494:pharmacology*
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D011812:Quinuclidines; C076851:L 703606; D013373:Substance P