Habenular Kiss1 Neurons Modulate the Serotonergic System in the Brain of Zebrafish
Habenular Kiss1 Neurons Modulate the Serotonergic System in the Brain of Zebrafish
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DOI：
10.1210/en.2012-1062
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发表时间：
2012-05-01
期刊：
影响因子：
4.8
通讯作者：
Parhar, Ishwar S.
中科院分区：
文献类型：
--
作者：
Ogawa, Satoshi;Ng, Kai We;Parhar, Ishwar S.
Kiss 1/KISS 1基因最近被认为是生殖功能的有效下丘脑调节因子，特别是哺乳动物青春期的开始。在斑马鱼（Danio rerio）中，有两种kiss 1同源物（kiss 1和kiss 2）在大脑中表达：下丘脑核中的kiss 2表达神经元被认为是生殖的有效调节者，而缰中的kiss 1表达神经元的作用仍然未知。我们首先分析了Kiss 1 mRNA在转基因斑马鱼中的表达，其中缰核-脚间核（IPN）通路用绿色荧光蛋白标记，并且我们将生物胞素神经示踪剂应用于缰核中，表明Kiss 1神经元向腹侧IPN的神经元投射的存在。因此，我们推测kiss 1神经元可能调节中缝核内的多巴胺能系统。然而，激光显微切割，然后实时PCR显示的Kiss 1受体（kissr 1）mRNA的表达在缰核和腹侧IPN，但不是在背侧IPN或中缝核的多巴胺能神经元。双荧光原位杂交结果显示，缰核中kiss 1和kissr 1 mRNA共表达。Kiss 1基因的表达水平显著降低（0.3 ~ 0.5倍，P < 0.001），而c-fos基因的表达水平升高（接近3倍，P < 0.05），提示kiss 1基因存在自分泌调节。Kiss 1显著增加中缝核c-fos mRNA水平（2.5倍，P < 0.001）和参与5-羟色胺水平调节的基因（pet 1和slc 6a 4a; 3.3和2.2倍，P < 0.01）。这些结果表明，自分泌调节的缰Kiss 1神经元间接调节中缝核的突触能系统通过在斑马鱼的IPN。（内分泌学153：2398-2407，2012）
The Kiss1/KISS1 gene has recently been implicated as a potent hypothalamic regulator of reproductive functions, in particular, the onset of puberty in mammals. In zebrafish (Danio rerio), there are two kiss1 homologues (kiss1 and kiss2) expressed in the brain: Kiss2-expressing neurons in the hypothalamic nuclei are considered potent regulators of reproduction, whereas the role of Kiss1-expressing neurons in the habenula remains unknown. We first analyzed the expression of kiss1 mRNA in a transgenic zebrafish, in which the habenula-interpeduncular nucleus (IPN) pathway is labelled with green fluorescent protein, and our application of a biocytin neural tracer into the habenula showed the presence of neuronal projections of Kiss1 neurons to the ventral IPN. Therefore, we speculated that kiss1 neurons might regulate the serotonergic system in the raphe. However, laser microdissection followed by real-time PCR revealed the expression of Kiss1 receptor (kissr1) mRNA in the habenula and the ventral IPN but not in the dorsal IPN or the serotonergic neurons in the raphe nuclei. Dual-fluorescent in situ hybridization revealed the coexpression of kiss1 and kissr1 mRNA in the habenula. Administration of Kiss1 significantly decreased the level of kiss1 mRNA (0.3- to 0.5-fold, P < 0.001), but the level of c-fos mRNA was increased (similar to 3-fold, P < 0.05) in the ventral habenula, suggesting that there is autocrine regulation of the kiss1 gene. Kiss1 administration significantly increased the c-fos mRNA levels in the raphe nuclei (2.5-fold, P < 0.001) and genes involved in the regulation of serotonin levels (pet1 and slc6a4a; 3.3-and 2.2-fold, P < 0.01). These findings suggest that the autocrine-regulated habenular Kiss1 neurons indirectly regulate the serotonergic system in the raphe nuclei through the IPN in the zebrafish. (Endocrinology 153: 2398-2407, 2012)