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多巴胺D1受体激活调节放射状胶质细胞中雌激素合成基因芳香化酶B的表达。

Dopamine D1 receptor activation regulates the expression of the estrogen synthesis gene aromatase B in radial glial cells.

作者信息

Xing Lei, McDonald Heather, Da Fonte Dillon F, Gutierrez-Villagomez Juan M, Trudeau Vance L

机构信息

Department of Biology, Centre for Advanced Research in Environmental Genomics, University of Ottawa Ottawa, ON, Canada.

出版信息

Front Neurosci. 2015 Sep 2;9:310. doi: 10.3389/fnins.2015.00310. eCollection 2015.

Abstract

Radial glial cells (RGCs) are abundant stem-like non-neuronal progenitors that are important for adult neurogenesis and brain repair, yet little is known about their regulation by neurotransmitters. Here we provide evidence for neuronal-glial interactions via a novel role for dopamine to stimulate RGC function. Goldfish were chosen as the model organism due to the abundance of RGCs and regenerative abilities of the adult central nervous system. A close anatomical relationship was observed between tyrosine hydroxylase-positive catecholaminergic cell bodies and axons and dopamine-D1 receptor expressing RGCs along the ventricular surface of telencephalon, a site of active neurogenesis. A primary cell culture model was established and immunofluorescence analysis indicates that in vitro RGCs from female goldfish retain their major characteristics in vivo, including expression of glial fibrillary acidic protein and brain lipid binding protein. The estrogen synthesis enzyme aromatase B is exclusively found in RGCs, but this is lost as cells differentiate to neurons and other glial types in adult teleost brain. Pharmacological experiments using the cultured RGCs established that specific activation of dopamine D1 receptors up-regulates aromatase B mRNA through a cyclic adenosine monophosphate-dependent molecular mechanism. These data indicate that dopamine enhances the steroidogenic function of this neuronal progenitor cell.

摘要

放射状胶质细胞(RGCs)是丰富的干细胞样非神经元祖细胞,对成体神经发生和脑修复很重要,但关于神经递质对它们的调节作用却知之甚少。在这里,我们通过多巴胺刺激RGC功能的新作用为神经元 - 胶质细胞相互作用提供了证据。由于RGCs丰富以及成体中枢神经系统具有再生能力,金鱼被选为模式生物。在端脑的脑室表面,即活跃神经发生的部位,观察到酪氨酸羟化酶阳性的儿茶酚胺能细胞体和轴突与表达多巴胺 - D1受体的RGCs之间存在密切的解剖学关系。建立了原代细胞培养模型,免疫荧光分析表明,来自雌性金鱼的体外RGCs保留了它们在体内的主要特征,包括胶质纤维酸性蛋白和脑脂质结合蛋白的表达。雌激素合成酶芳香化酶B仅在RGCs中发现,但在成年硬骨鱼脑中,随着细胞分化为神经元和其他胶质细胞类型,这种酶会消失。使用培养的RGCs进行的药理学实验表明,多巴胺D1受体的特异性激活通过环磷酸腺苷依赖性分子机制上调芳香化酶B mRNA。这些数据表明多巴胺增强了这种神经元祖细胞的类固醇生成功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3bf/4557113/a4e599d4c994/fnins-09-00310-g0001.jpg

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