Deficiency of Serotonin in Raphe Neurons and Altered Behavioral Responses in Tryptophan Hydroxylase 2-Knockout Medaka (Oryzias latipes)
Deficiency of Serotonin in Raphe Neurons and Altered Behavioral Responses in Tryptophan Hydroxylase 2-Knockout Medaka (Oryzias latipes)
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DOI：
10.1089/zeb.2017.1452
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发表时间：
2017-12-01
期刊：
影响因子：
2
通讯作者：
Kinoshita, Masato
中科院分区：
文献类型：
--
作者：
Ansai, Satoshi;Hosokawa, Hiroshi;Kinoshita, Masato
5-羟色胺（5-HT）是一种生物活性的单胺，在动物的中枢和外周神经系统中作为神经递质。硬骨鱼类在脑干的中缝核中具有5-HT能神经元;然而，5-HT在硬骨鱼中缝核神经元中的作用在很大程度上仍然未知。在这里，我们建立了一个青鳉（Oryzias latipes）菌株与有针对性的色氨酸羟化酶2（tph 2）基因，参与中缝核5-HT的合成中断。免疫组织化学和质谱分析显示，纯合子突变体（tph 2（13/13））缺乏在中缝神经元合成5-HT的能力。为了研究5-HT缺乏对成年鱼行为的影响，对突变鱼进行了5种行为模式（潜水、旷场、明暗过渡、咬镜和两鱼社会互动）。纯合突变引起的冻结反应的持续时间较长，在所有检查的范例，并减少了条目的数量，以顶部地区的潜水测试。此外，突变体表现出减少男性的镜子咬和女性之间的直接社会互动的接触时间增加。这些结果表明，这种tph 2基因敲除青鳉作为一个很好的模型，以分析在中缝神经元5-HT缺乏的影响。
Serotonin (5-hydroxytryptamine [5-HT]) is a bioactive monoamine that acts as a neurotransmitter in the central and peripheral nervous system of animals. Teleost fish species have serotonergic neurons in the raphe nuclei of the brainstem; however, the role of 5-HT in the raphe neurons in teleost fish remains largely unknown. Here, we established a medaka (Oryzias latipes) strain with targeted disruption of tryptophan hydroxylase 2 (tph2) gene that is involved in the 5-HT synthesis in the raphe nuclei. Immunohistochemistry and mass spectrometry analysis revealed that the homozygous mutants (tph2(13/13)) lacked the ability to synthesize 5-HT in the raphe neurons. To investigate the effects of 5-HT deficiency in adult behaviors, the mutant fish were subjected to five behavioral paradigms (diving, open-field, light-dark transition, mirror-biting, and two-fish social interaction). The homozygous mutation caused a longer duration of freezing response in all examined paradigms and reduced the number of entries to the top area in the diving test. In addition, the mutants exhibited a decreased number of mirror-biting in the males and an increased contact time in direct social interaction between the females. These results indicate that this tph2-knockout medaka serves as a good model to analyze the effects of 5-HT deficiency in the raphe neurons.