NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium.
In the CNS, ATP is released upon injury and promotes neuroproliferation via purinergic receptors. In the olfactory epithelium, ATP promotes the synthesis and release of neurotrophic factor NPY in neonates and induces neuroproliferation in neonatal and adult mice. We tested the hypothesis that NPY is involved in ATP-induced neuroproliferation in adult mice olfactory epithelium. Intranasal instillation of ATP significantly increased protein levels and number of NPY(+) cells. Pre-intranasal instillation of purinergic receptor antagonist PPADS significantly reduced ATP-induced upregulation of NPY. Intranasal instillation of NPY-Y1 receptor antagonist BIBP3226 following ATP instillation significantly inhibited the ATP-induced increase in BrdU incorporation, suggesting that NPY is released after ATP instillation and activates Y1 receptors to promote neuroproliferation. These data indicate that ATP initiates neuroproliferation via NPY upregulation, NPY release, and Y1 receptor activation, and suggests that the olfactory epithelium is good model to study neuroregenerative mechanisms in the CNS.
Jia
Cuihong
C
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
Hegg
Colleen Cosgrove
CC
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008959:Models, Neurological; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000187:drug effects / Q000502:physiology*; D058914:Purinergic Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology
C092926:BIBP 3226; D009478:Neuropeptide Y; C507698:Npy1r protein, mouse; D058914:Purinergic Antagonists; D017476:Receptors, Neuropeptide Y; D011983:Receptors, Purinergic; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; D001120:Arginine