Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio).

Kisspeptins modulate the biology of multiple populations of gonadotropin-releasing hormone neurons during embryogenesis and adulthood in zebrafish (Danio rerio).
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DOI:
10.1371/journal.pone.0104330
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Wayne NL
Wayne NL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zhao Y;Lin MC;Mock A;Yang M;Wayne NL

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Kisspeptin 1(Kiss 1基因的产物)是通过调节哺乳动物促性腺激素释放激素(GnRH)神经系统来开启青春期并维持生育力的关键神经肽。Kiss 1和kisspeptin受体(GPR 54/Kiss 1 r)的失活突变与青春期失败和不育有关。Kiss 2是Kiss 1的旁系同源基因,最近在包括斑马鱼在内的几种脊椎动物中被发现。使用我们的转基因斑马鱼模型系统,其中GnRH 3启动子驱动祖母绿绿色荧光蛋白的表达,我们研究了kisspeptins对胚胎发育过程中GnRH神经元系统发育和成年期电活动的影响。定量PCR检测结果显示,kiss 1和kiss 2 mRNA水平的受精后1天,增加整个胚胎和幼虫发育。早期用Kiss 1或Kiss 2处理表明,两种kisspeptins刺激位于周围神经系统的三叉神经GnRH 3神经元的增殖。然而,只有Kiss 1,而不是Kiss 2,刺激中枢神经系统中的终末神经和下丘脑的GnRH 3神经元群的增殖。突触囊泡蛋白2的免疫组织化学分析表明,Kiss 1,但不是Kiss 2,增加突触接触的细胞体和沿着终末神经-GnRH 3神经元的过程中胚胎发育。在完整的成年斑马鱼脑中,全细胞膜片钳记录的GnRH 3神经元的视前区和下丘脑显示相反的影响Kiss 1和Kiss 2的自发动作电位放电频率和膜电位。Kiss 1增加峰频率和去极化膜电位,而Kiss 2抑制峰频率和超极化膜电位。我们的结论是,在斑马鱼,Kiss 1是主要的刺激剂促性腺激素释放激素3神经元的发育在胚胎和激活剂刺激垂体神经元的活动在成人,而Kiss 2起着额外的作用,刺激胚胎发育的三叉神经元的人口,但RFamide抑制电活动的垂体促性腺激素释放激素3神经元在成人。
Kisspeptin1 (product of the Kiss1 gene) is the key neuropeptide that gates puberty and maintains fertility by regulating the gonadotropin-releasing hormone (GnRH) neuronal system in mammals. Inactivating mutations in Kiss1 and the kisspeptin receptor (GPR54/Kiss1r) are associated with pubertal failure and infertility. Kiss2, a paralogous gene for kiss1, has been recently identified in several vertebrates including zebrafish. Using our transgenic zebrafish model system in which the GnRH3 promoter drives expression of emerald green fluorescent protein, we investigated the effects of kisspeptins on development of the GnRH neuronal system during embryogenesis and on electrical activity during adulthood. Quantitative PCR showed detectable levels of kiss1 and kiss2 mRNA by 1 day post fertilization, increasing throughout embryonic and larval development. Early treatment with Kiss1 or Kiss2 showed that both kisspeptins stimulated proliferation of trigeminal GnRH3 neurons located in the peripheral nervous system. However, only Kiss1, but not Kiss2, stimulated proliferation of terminal nerve and hypothalamic populations of GnRH3 neurons in the central nervous system. Immunohistochemical analysis of synaptic vesicle protein 2 suggested that Kiss1, but not Kiss2, increased synaptic contacts on the cell body and along the terminal nerve-GnRH3 neuronal processes during embryogenesis. In intact brain of adult zebrafish, whole-cell patch clamp recordings of GnRH3 neurons from the preoptic area and hypothalamus revealed opposite effects of Kiss1 and Kiss2 on spontaneous action potential firing frequency and membrane potential. Kiss1 increased spike frequency and depolarized membrane potential, whereas Kiss2 suppressed spike frequency and hyperpolarized membrane potential. We conclude that in zebrafish, Kiss1 is the primary stimulator of GnRH3 neuronal development in the embryo and an activator of stimulating hypophysiotropic neuron activities in the adult, while Kiss2 plays an additional role in stimulating embryonic development of the trigeminal neuronal population, but is an RFamide that inhibits electrical activity of hypophysiotropic GnRH3 neurons in the adult.
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