Spexin (SPX) is an evolutionarily conserved neuropeptide that is expressed in the mammalian brain and peripheral tissue. Two orthologs are present in the teleost, SPX1 and SPX2. SPX1 is involved in reproduction and food intake. Recently, SPX1 neurons have been found to be located in the specific nuclei of dorsal habenula (dHb) and to project into the interpeduncular nucleus (IPN), in which galanin receptor 2a/2b (GALR2a/2b) expression was also observed. This indicates that habenula SPX1 neurons may interact with GALR2a/2b in the IPN; however, the function of SPX1 in the dHb-IPN neuronal circuit remains unknown. To determine the role of SPX1 in the dHb-IPN neural circuit, we generated transgenic zebrafish overexpressing SPX1 specifically in the dHb. We found that transgenic zebrafish overexpressing SPX1 in the dHb had anxiolytic behaviors compared with their wildtype siblings. Furthermore, quantitative PCR revealed that mRNA expression of galr2a and galr2b in the IPN and serotonin-related genes in the raphe was upregulated in the brains of transgenic zebrafish. Taken together, our data suggest that SPX1 function in the dHb-IPN neural circuits is implicated in the regulation of anxiety behaviors via modulation of the serotoninergic system in zebrafish.

中文翻译：

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Spexin 1在背侧哈贝努拉中的过表达减少了斑马鱼的焦虑。

Spexin（SPX）是一种在哺乳动物大脑和外周组织中表达的进化保守的神经肽。硬骨鱼中有两个直系同源物，即SPX1和SPX2。SPX1与生殖和食物摄入有关。最近，已发现SPX1神经元位于背侧ha管（dHb）的特定核中，并伸入椎间隙间核（IPN），其中还观察到甘丙肽受体2a / 2b（GALR2a / 2b）表达。这表明ha嘴SPX1神经元可能与IPN中的GALR2a / 2b相互作用。但是，SPX1在dHb-IPN神经元回路中的功能仍然未知。为了确定SPX1在dHb-IPN神经回路中的作用，我们生成了在dHb中过表达SPX1的转基因斑马鱼。我们发现，与野生型同胞相比，dHb中过表达SPX1的转基因斑马鱼具有抗焦虑行为。此外，定量PCR揭示了转基因斑马鱼的大脑中IPN中galr2a和galr2b的mRNA表达以及中缝中血清素相关基因的表达上调。综上所述，我们的数据表明，dHb-IPN神经回路中的SPX1功能通过调节斑马鱼的5-羟色胺能系统而参与了焦虑行为的调节。