Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell-death in rodents

Abstract

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 (10 μg/mouse, i.c.v.) significantly decreased spontaneous alternation, an effect which was in turn inhibited by NmU (0.5 nmol/mouse, i.c.v.). Real-time PCR-based experiments indicated that NmU did not affect the mRNA level of IL-1β 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-1β. 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.