Sexually Dimorphic Neuropeptide B Neurons in Medaka Exhibit Activated Cellular Phenotypes Dependent on Estrogen

Sexually Dimorphic Neuropeptide B Neurons in Medaka Exhibit Activated Cellular Phenotypes Dependent on Estrogen
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DOI:
10.1210/en.2019-00030
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发表时间:
2019-04-01
期刊:
影响因子:
4.8
通讯作者:
Okubo, Kataaki
Okubo, Kataaki
中科院分区:
医学2区
文献类型:
--
作者:
Kikuchi, Yukiko;Hiraki-Kajiyama, Towako;Okubo, Kataaki

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硬骨鱼的大脑和行为在一生中都具有高度的性可塑性,但其潜在的神经机制在很大程度上是未知的。在对青海硬骨鱼(Oryzias Latipe)脑形态的研究中,我们发现在大细胞视前核内有明显的大神经元,雌性比雄性多见。对性反转青竹的检查表明,这些神经元的性二态丰度依赖于性腺表型,但与性染色体组成无关。大多数女性的这些神经元产生神经肽B(NPB),但男性没有。众所周知,神经肽B的表达是雌激素依赖的,与女性的性接受能力有关。在表型分析中,雌性特有的NPB神经元有一个大的常染核,细胞质丰富,含有丰富的粗面内质网,总体转录活性增强,典型的自发规则放电模式。这些表型,可能是细胞激活的指标,被卵巢切除减弱,并通过雌激素替代恢复。此外,在接受雌激素治疗的成年男性中,NPB表达神经元的群体出现,不是通过成年硬骨鱼大脑中频繁发生的神经发生,而是通过激活先前存在的、静止的男性对应神经元。综上所述,我们的结果表明,性二形视前NPB神经元的形态、转录和电生理表型高度依赖于雌激素,并且可以在雌性和雄性模式之间切换。视前NPB神经元的这些特性可能是硬骨鱼大脑和行为的性别分化和可塑性的神经机制的基础。
Brain and behavior of teleosts are highly sexually plastic throughout life, yet the underlying neural mechanisms are largely unknown. On examining brain morphology in the teleost medaka (Oryzias latipes), we identified distinctively large neurons in the magnocellular preoptic nucleus that occurred much more abundantly in females than in males. Examination of sex-reversed medaka showed that the sexually dimorphic abundance of these neurons is dependent on gonadal phenotype, but independent of sex chromosome complement. Most of these neurons in females, but none in males, produced neuropeptide B (Npb), whose expression is known to be estrogen-dependent and associated with female sexual receptivity. In phenotypic analysis, the female-specific Npb neurons had a large euchromatic nucleus with an abundant cytoplasm containing plentiful rough endoplasmic reticulum, exhibited increased overall transcriptional activity, and typically displayed a spontaneous regular firing pattern. These phenotypes, which are probably indicative of cellular activation, were attenuated by ovariectomy and restored by estrogen replacement. Furthermore, the population of Npb-expressing neurons emerged in adult males treated with estrogen, not through frequently occurring neurogenesis in the adult teleost brain, but through the activation of preexisting, quiescent male counterpart neurons. Collectively, our results demonstrate that the morphological, transcriptional, and electrophysiological phenotypes of sexually dimorphic preoptic Npb neurons are highly dependent on estrogen and can be switched between female and male patterns. These properties of the preoptic Npb neurons presumably underpin the neural mechanism for sexual differentiation and plasticity of brain and behavior in teleosts.