Differential effect of oestradiol and astroglia-conditioned media on the growth of hypothalamic neurons from male and female rat brains

Differential effect of oestradiol and astroglia-conditioned media on the growth of hypothalamic neurons from male and female rat brains
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DOI:
10.1046/j.1460-9568.2000.00120.x
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发表时间:
2000-07-01
影响因子:
3.4
通讯作者:
Carrer, HF
Carrer, HF
中科院分区:
医学3区
文献类型:
--
作者:
Cambiasso, MJ;Colombo, JA;Carrer, HF

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为了确定是否从不同的中枢神经系统区域的可溶性产品不同的能力,以支持雌激素刺激的神经突起的生长,培养下丘脑神经元从性别分离的胚胎与星形胶质细胞条件培养基(CM)来自皮质,纹状体和中脑,有或没有17-β-雌二醇100 nm添加到培养基中。体外培养48小时后,通过形态计量学分析对神经突生长进行定量。中脑的星形胶质细胞-CM(下丘脑神经元轴突的靶点)在男性中诱导了最大的轴突反应,在这种情况下,雌二醇只能表现出促轴突生长的作用。另一方面,星形胶质细胞-CM的区域,不接受下丘脑腹内侧投射抑制轴突生长。下丘脑神经元的星形胶质细胞-CM和雌二醇的反应中的性别差异被发现,从女性胎儿的神经元的生长增加了星形胶质细胞-CM从中脑,但没有neuritogenic效应可以证明雌二醇在这些文化。印迹免疫结合证明了下丘脑神经元培养物中存在神经营养因子受体;这些培养物的Western印迹分析表明,雌二醇增加了trkB和IGF-I R-β的浓度,而未检测到trkA,trkC的浓度未被修改。这些结果支持靶区域产生刺激投射神经元轴突生长的某些因子的假设,并进一步表明,在雄性的情况下,这种效应受雌二醇调节,可能通过trkB和IGF-I受体的上调介导。
To determine whether soluble products from different CNS regions differ in their ability to support oestrogen-stimulated neurite growth, hypothalamic neurons from sexually segregated embryos were cultured with astroglia-conditioned medium (CM) derived from cortex, striatum and mesencephalon, with or without 17-beta-oestradiol 100 nm added to the medium. After 48 h in vitro, neurite outgrowth was quantified by morphometric analysis. Astroglia-CM from mesencephalon (a target for the axons of hypothalamic neurons) induced the greatest axogenic response in males and in this case only a neuritogenic effect could be demonstrated for oestradiol. On the other hand, astroglia-CM from regions that do not receive projections from ventromedial hypothalamus inhibited axon growth. A sexual difference in the response of hypothalamic neurons to astroglia-CM and oestradiol was found; growth of neurons from female foetuses was increased by astroglia-CM from mesencephalon, but no neuritogenic effect could be demonstrated for oestradiol in these cultures. Blot immunobinding demonstrated the presence of receptors for neurotrophic factors in cultures of hypothalamic neurons; Western blot analysis of these cultures demonstrated that oestradiol increased the concentration of trkB and IGF-I R-beta, whereas trkA was not detected and the concentration of trkC was not modified. These results support the hypothesis that target regions produce some factor(s) that stimulate the growth of axons from projecting neurons and further indicate that in the case of males this effect is modulated by oestradiol, perhaps mediated through the upregulation of trkB and IGF-I receptors.