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首页> 外文期刊>The European Journal of Neuroscience >Distinct populations of hypothalamic dopaminergic neurons exhibit differential responses to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3).
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Distinct populations of hypothalamic dopaminergic neurons exhibit differential responses to brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3).

机译:下丘脑多巴胺能神经元的不同群体表现出对脑源性神经营养因子(BDNF)和Neurotrophin-3(NT3)的不同反应。

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We have previously demonstrated that differentiation of hypothalamic dopaminergic (DA) neurons can be induced in culture by their pituitary intermediate lobe target cells, through both membrane and diffusible factors. We also showed that subpopulations of DA neurons from the arcuate nucleus only, not the periventricular area, can respond to the target. Here we investigated the possibility that both neuronal subsets could also respond differentially to brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT3). Addition of NT3, but not BDNF, enhanced growth and branching of neurites, tyrosine hydroxylase (TH) as well as increasing levels of cultured arcuate DA neurons. Conversely, BDNF, but not NT3, affected the same parameters in cultured periventricular DA neurons. The neurotrophins thus affect DA neurons in a structure and neuronal type-selective manner, since general neuronal markers were not affected by either neurotrophin. Neurotrophin effects were reversed by addition of specific antibodies directed against them or their respective receptors, TrkB or TrkC. By themselves, the antibodies inhibited development of DA neurons below that of control cultures, suggesting involvement of endogenous neurotrophins. BDNF and NT3 were indeed found in both arcuate and periventricular neurons and in the intermediate lobe. BDNF was always present as the mature peptide. The mature form of NT3 was only detected in the periventricular area; a precursor-like heavier form was present in all tissues studied. The present data suggest that NT3, but not BDNF, could participate in the differentiating action of intermediate lobe cells on arcuate DA neurons.
机译:先前我们已经证明,下丘脑多巴胺能(DA)神经元的分化可以通过其垂体中间叶靶细胞通过膜和扩散因子在培养中诱导。我们还表明,仅来自弓形核的DA神经元亚群(而不是脑室周围区域)可以对靶标作出反应。在这里,我们调查了两个神经元子集也可能对脑源性神经营养因子(BDNF)或Neurotrophin-3(NT3)做出不同反应的可能性。 NT3而不是BDNF的添加,增强了神经突,酪氨酸羟化酶(TH)的生长和分支,并提高了弓形DA神经元的培养水平。相反,BDNF而非NT3会影响培养的脑室周围DA神经元的相同参数。因此,神经营养素以结构和神经元类型选择性的方式影响DA神经元,因为一般的神经元标记不受任何一种神经营养素的影响。通过添加针对它们或它们各自的受体TrkB或TrkC的特异性抗体,可以逆转神经营养蛋白的作用。抗体自身抑制DA神经元的发育低于对照培养物,表明内源性神经营养蛋白的参与。确实在弓形和脑室周围神经元以及中叶中都发现了BDNF和NT3。 BDNF始终作为成熟肽存在。 NT3的成熟形式仅在脑室周围区域检测到。在所有研究的组织中均存在类似前体的较重形式。目前的数据表明NT3,但不是BDNF,可以参与弓形DA神经元的中间叶细胞的分化作用。

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