Neuropeptide Y expression in mouse hippocampus and its role in neuronal excitotoxicity.
OBJECTIVE
To investigate neuropeptide Y (NPY) expression in mouse hippocampus within early stages of kainic acid (KA) treatment and to understand its role in neuronal excitotoxicity.


METHODS
NPY expression in the hippocampus within early stages of KA intraperitoneal (ip) treatment was detected by immunohistochemistry (IHC) and in situ hybridization (ISH) methods. The role of NPY and Y5, Y2 receptors in excitotoxicity was analyzed by terminal deoxynucleotidyl transferase-mediated UTP nick end-labeling (TUNEL) assay.


RESULTS
Using IHC assay, in granule cell layer of the dentate gyrus (DG), NPY positive signals appeared 4 h after KA injection, reached the peak at 8 h and leveled off at 16 and 24 h. In CA3, no positive signal was found within the first 4 h after KA injection, but strong signal appeared at 16 and 24 h. No noticeable signal was detected in CA1 at all time points after KA injection. Using the ISH method, positive signals were detected at 4, 8, and 16 h in CA3, CA1, and hilus. In DG, much stronger ISH signals were detected at 4 h, but leveled off at 8 and 16 h. TUNEL analysis showed that intracerebroventricularly (icv) infusion of NPY and Y5, Y2 receptor agonists within 8 h after KA insult with proper dose could remarkably rescue pyramidal neurons in CA3 and CA1 from apoptosis.


CONCLUSIONS
NPY is an important anti-epileptic agent. The preceding elevated expression of NPY in granule cell layer of DG after KA injection might partially explain its different excitotoxicity-induced apoptotic responses in comparison with the pyramidal neurons from CA3 and CA1 regions. NPY can not only reduce neuronal excitability but also prevent excitotoxicity-induced neuronal apoptosis in a time- and dose-related way by activation of Y5 and Y2 receptors.
Wu
Yong-fei
YF
State Key Laboratory of Forensic Sciences, State Key Laboratory of Environment and Disease Related Genes, Xi'an Jiaotong University College of Medicine, Xi'an 710061, China.
Li
Sheng-bin
SB
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D018891:Dentate Gyrus / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D009478:Neuropeptide Y / Q000378:metabolism* / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000187:drug effects; D013997:Time Factors
D000927:Anticonvulsants; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; C100568:neuropeptide Y5 receptor; D007608:Kainic Acid