title: Nramp1 is expressed in neurons and is associated with behavioural and immune responses to stress.
abstract: The gene Nramp1 encoding the natural resistance-associated macrophage protein (Nramp1) influences susceptibility to intracellular infections and autoimmune diseases, and the humoral response to stress. Nramp1 functions as a proton/divalent cation antiporter in the membranes of late endosomes/lysosomes, regulating cytoplasmic iron levels in macrophages. The Drosophila homologue of Nramp1 is expressed in sensory neurons and macrophages, and influences taste behaviour directly through divalent cation transport. Here we demonstrate that murine Nramp1 is also expressed on neurons as well as microglial cells in the brain and influences the behavioural response to stress, hypothalamus-pituitary-adrenal (HPA) axis activation and mortality following Toxoplasma gondii infection in control and prestressed mice. We hypothesise that, although differences in HPA activation translate into differences in adrenal enlargement and basal circulating corticosterone levels, the primary influence of Nramp1 is at the level of the neuronal response to stress. These results provide new insight into the possible roles of divalent cation transporters of the Nramp gene family in regulating metal ion homeostasis in the brain and its pathological implications.
authors.affiliation: Wellcome Trust Centre for Molecular Mechanisms in Disease, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Evans
authors.forename: M S
authors.initials: MS
authors.lastname: Harbuz
authors.forename: T
authors.initials: T
authors.lastname: Ostenfeld
authors.forename: A
authors.initials: A
authors.lastname: Norrish
authors.forename: J M
authors.initials: JM
authors.lastname: Blackwell
mesh_terms: D000311:Adrenal Glands / Q000502:physiology / Q000503:physiopathology; D000818:Animals; D000917:Antibody Formation; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D027682:Cation Transport Proteins; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000503:physiopathology*; D014122:Toxoplasma; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003346:Corticotropin-Releasing Hormone; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1