Evidence that IGF-I acts as an autocrine/paracrine growth factor in the magnocellular neurosecretory system: neuronal synthesis and induction of axonal sprouting.
Evidence that IGF-I acts as an autocrine/paracrine growth factor in the magnocellular neurosecretory system: neuronal synthesis and induction of axonal sprouting.
复制标题
IGF-I 在大细胞神经分泌系统中作为自分泌/旁分泌生长因子的证据：神经元合成和轴突萌芽的诱导。
DOI：
10.1006/exnr.1999.7189
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Paden,CM
中科院分区：
文献类型：
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作者：
Zhou,X;Herman,JP;Paden,CM
成熟催产素（OT）和加压素（VP）神经元的大细胞神经分泌系统（MNS）进行轴突生长的能力意味着一个或多个生长因子可能是活跃的成人MNS，但很少有人知道他们可能的身份。一种这样的潜在因子是胰岛素样生长因子I（IGF-I）。我们研究了IGF-I mRNA和IGF-I免疫反应性（IGF-I-ir）在成熟MNS中的表达，并确定了OT和VP神经元对IGF-I下丘脑植入物的体内反应。原位杂交显示，IGF-I的mRNA在视上核（SON）和室旁核（PVN）的成年雄性大鼠中度标记。RT-PCR分析证实了真实的IGF-I mRNA的基底下丘脑提取物的存在。微弱的IGF-I-IR中检测到分散的大细胞神经元内的PVN和SON的正常大鼠，但IGF-I-IR是更强烈的，大多数的MNS神经元，包括那些在副核免疫反应性的大鼠给予秋水仙素的切片，作为一些小细胞神经元的PVN。共聚焦显微镜显示，IGF-I-IR存在于OT和VP神经元，但VP神经元包含最强烈的IGF-I-IR。最后，OT，但不是VP纤维的戏剧性的生长反应，观察到植入后的聚合物棒含有IGF-I到下丘脑。一个密集的OT纤维丛沿着套管轨道生长，OT纤维侵入SON腹侧的软脑膜，并环绕吻侧大脑动脉。据我们所知，这是第一次证明成熟的OT神经元轴突发芽响应于一个确定的生长因子和发芽响应于外源性IGF-I在成人中枢神经系统中的第一个直接证明。这些结果表明，IGF-I合成和运输的成年MNS神经元，它可能作为一个自分泌和/或旁分泌生长因子。
The ability of mature oxytocinergic (OT) and vasopressinergic (VP) neurons of the magnocellular neurosecretory system (MNS) to undergo axonal growth implies that one or more growth factors may be active in the adult MNS, yet little is known regarding their possible identity. One such potential factor is insulin-like growth factor I (IGF-I). We have examined the expression of IGF-I mRNA and IGF-I-immunoreactivity (IGF-I-ir) in the mature MNS and have also determined the in vivo response of OT and VP neurons to hypothalamic implants of IGF-I. In situ hybridization revealed moderate labeling of IGF-I mRNA in both the supraoptic (SON) and the paraventricular (PVN) nuclei of adult male rats. RT-PCR analysis confirmed the presence of authentic IGF-I mRNA in extracts of the basal hypothalamus. Faint IGF-I-ir was detected in scattered magnocellular neurons within both the PVN and the SON of normal rats, but IGF-I-ir was much more intense and the majority of MNS neurons including those in the accessory nuclei were immunoreactive in sections from rats given colchicine, as were some parvocellular neurons in the PVN. Confocal microscopy revealed that IGF-I-ir was present in both OT and VP neurons, but VP neurons contained the most intense IGF-I-ir. Finally, a dramatic growth response of OT but not of VP fibers was observed following implantation of polymer rods containing IGF-I into the hypothalamus. A dense OT fiber plexus grew along the cannula track and OT fibers invaded the leptomeninges ventral to the SON and encircled the rostral cerebral artery. To our knowledge this is the first demonstration of axonal sprouting by mature OT neurons in response to an identified growth factor and the first direct demonstration of sprouting in response to exogenous IGF-I in the adult CNS. These findings suggest that IGF-I is synthesized and transported by adult MNS neurons where it may act as an autocrine and/or paracrine growth factor.