首页> 外文期刊>Neuroscience: An International Journal under the Editorial Direction of IBRO >INTRACELLULAR NOGO-A FACILITATES INITIATION OF NEURITE FORMATION IN MOUSE MlDBRAIN NEURONS IN VITRO
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INTRACELLULAR NOGO-A FACILITATES INITIATION OF NEURITE FORMATION IN MOUSE MlDBRAIN NEURONS IN VITRO

机译:鞘内NOGO-A促进小鼠小脑神经元中神经胶质的形成

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Nogo-A is a transmembrane protein originally discovered in myelin, produced by postnatal CNS oligoden-drocytes. Nogo-A induces growth cone collapse and inhibition of axonal growth in the injured adult CNS. In the intact CNS, Nogo-A functions as a negative regulator of growth and plasticity. Nogo-A is also expressed by certain neurons. Neuronal Nogo-A depresses long-term potentiation in the hippocampus and modulates neurite adhesion and fascicu-lation during development in mice. Here we show that Nogo-A is present in neurons derived from human midbrain (Lund human mesencephalic (LUHMES) cell line), as well as in embryonic and postnatal mouse midbrain (dopaminergic) neurons. In LUHMES cells, Nogo-A was upregulated threefold upon differentiation and neurite extension. Nogo-A was localized intracellularly in differentiated LUHMES cells. Cultured midbrain (dopaminergic) neurons from Nogo-A knock-out mice exhibited decreased numbers of neurites and branches when compared with neurons from wild-type (WT) mice. However, this phenotype was not observed when the cultures from WT mice were treated with an antibody neutralizing plasma membrane Nogo-A. In vivo, neither the regeneration of nigrostriatal tyrosine hydroxylase fibers, nor the survival of nigral dopaminergic neurons after partial 6-hydroxydopamine lesions was affected by Nogo-A deletion. These results indicate that during maturation of cultured midbrain (dopaminergic) neurons, intracellular Nogo-A supports neurite growth initiation and branch formation.
机译:Nogo-A是最初在髓磷脂中发现的一种跨膜蛋白,由出生后的CNS少突胶质细胞产生。 Nogo-A在受伤的成年中枢神经系统中诱导生长锥塌陷并抑制轴突生长。在完整的中枢神经系统中,Nogo-A充当生长和可塑性的负调节剂。 Nogo-A也由某些神经元表达。神经元Nogo-A抑制小鼠海马的长时程增强,并在小鼠发育过程中调节神经突的粘附和束缚。在这里,我们显示Nogo-A存在于源自人中脑(干人中脑(LUHMES)细胞系)的神经元中,以及存在于胚胎和出生后小鼠中脑(多巴胺能)的神经元中。在LUHMES细胞中,Nogo-A在分化和神经突延伸后被上调了三倍。 Nogo-A位于细胞内分化的LUHMES细胞中。与野生型(WT)小鼠的神经元相比,Nogo-A基因敲除小鼠的培养的中脑(多巴胺能)神经元显示出减少的神经突和分支数目。然而,当用抗体中和质膜Nogo-A处理WT小鼠的培养物时,未观察到该表型。在体内,Nogo-A缺失既不影响黑质纹状体酪氨酸羟化酶纤维的再生,也不影响6-羟基多巴胺部分损伤后黑质多巴胺能神经元的存活。这些结果表明,在培养的中脑(多巴胺能)神经元成熟期间,细胞内Nogo-A支持神经突生长的起始和分支的形成。

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