Evans C A, Harbuz M S, Ostenfeld T, Norrish A, Blackwell J M
Wellcome Trust Centre for Molecular Mechanisms in Disease, Wellcome Trust/MRC Building, Addenbrooke's Hospital, Cambridge, CB2 2XY, UK.
Neurogenetics. 2001 Mar;3(2):69-78. doi: 10.1007/s100480100105.
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.
编码天然抗性相关巨噬细胞蛋白（Nramp1）的基因Nramp1影响对细胞内感染和自身免疫性疾病的易感性以及对应激的体液反应。Nramp1作为晚期内体/溶酶体膜中的质子/二价阳离子反向转运体，调节巨噬细胞中的细胞质铁水平。Nramp1的果蝇同源物在感觉神经元和巨噬细胞中表达，并通过二价阳离子转运直接影响味觉行为。在这里，我们证明小鼠Nramp1也在大脑中的神经元以及小胶质细胞上表达，并影响对照小鼠和应激前小鼠在弓形虫感染后的应激行为反应、下丘脑-垂体-肾上腺（HPA）轴激活和死亡率。我们推测，尽管HPA激活的差异转化为肾上腺肿大和基础循环皮质酮水平的差异，但Nramp1的主要影响在于神经元对应激的反应水平。这些结果为Nramp基因家族的二价阳离子转运体在调节大脑中金属离子稳态及其病理意义方面的可能作用提供了新的见解。
