Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell-death in rodents.
Neuromedin U (NmU) is a neuropeptide isolated first from porcine spinal cord and later from many species. Although NmU receptors exist in the hippocampus, their function is unclear. In the present study, we examined the effects of NmU on lipopolysaccharide (LPS)-induced memory impairment and neuronal death in mice. In the Y-maze test, LPS (10mug/mouse, i.c.v.) significantly decreased spontaneous alternation, an effect which was in turn inhibited by NmU (0.5nmol/mouse, i.c.v.). Real-time PCR-based experiments indicated that NmU did not affect the mRNA level of IL-1beta or IL-6 increased by LPS, whereas it increased that of brain-derived neurotrophic factor (BDNF) in the hippocampus. K252a, an inhibitor of tyrosine kinase, inhibited the anti-amnesic effects of NmU. Furthermore, LPS-treated glia conditioned medium (GCM) induced neuronal death in cultured hippocampal neurons from E18 rats. Pretreatment with NmU of LPS-treated cultured glia prevented the effects of GCM. However, NmU had no effect on neuronal death induced by direct treatment of neurons with IL-1beta. We propose that NmU protects memory function and neuronal cell viability from neuroinflammation. These effects may be mediated by production of neuroprotective factors, such as BDNF, in glia.
Iwai
Takashi
T
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, Japan.
Iinuma
Yuki
Y
Kodani
Reiye
R
Oka
Jun-Ichiro
J
D000818:Animals; D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D003627:Data Interpretation, Statistical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000523:psychology*; D008070:Lipopolysaccharides; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology*; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles
D000893:Anti-Inflammatory Agents; D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009479:Neuropeptides; D013778:Tetrazolium Salts; D013844:Thiazoles; C056900:neuromedin U; D012313:RNA; D004247:DNA; D011335:Proadifen; C022616:thiazolyl blue