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Selective Expression of Nicotinic Receptor Sub-unit mRNA in Early Human Fetal Forebrain.
Frontiers in Molecular Neuroscience ( IF 3.5 ) Pub Date : 2020-04-14 , DOI: 10.3389/fnmol.2020.00072
Ayman Alzu'bi 1, 2 , William Middleham 1 , Mohammed Shoaib 1 , Gavin J Clowry 1
Affiliation  

Increasing evidence from animal and human studies indicate that exposure to nicotine during development, separated from the effects of smoking tobacco, can contribute to dysregulation of brain development including behavioral deficits. An RNAseq study of human fetal cerebral cortex demonstrated that 9 out of 16 genes for human nicotinic acetylcholine (ACh) receptor subunits are selectively expressed between 7.5 and 12 post-conceptional weeks (PCW). The most highly expressed subunit genes were CHNRA4 and CHNRB2, whose protein products combine to form the most ubiquitous functional receptor isoform expressed in the adult brain. They exhibited correlated expression in both RNAseq samples, and in tissue sections by in situ hybridization. Co-localization studies with other cortical markers suggest they are pre-dominantly expressed by post-mitotic glutamatergic neuron pre-cursors in both cortical plate and pre-subplate, rather than cortical progenitor cells or GABAergic interneuron pre-cursors. However, GABAergic interneuron progenitor cells in the ganglionic eminences do express these sub-units. CHNRA5 also showed moderate levels of expression and again favored post-mitotic neurons. Other subunits, e.g., CHRNA7, exhibited low but detectable levels of expression. CHRN genes found not to be expressed included genes for subunits usually considered muscle specific, e.g., CHNRA1, although some muscle specific gene expression was detected, for instance CHNRB1. Although there is little or no synthesis of acetylcholine by intrinsic cortical neurons, cholinergic fibers from basal forebrain innervate the cerebral cortex from 12 PCW at the latest. Acetylcholine may have a paracrine effect on radially migrating cortical neurons and GABAergic interneuron progenitors.



中文翻译:

早期人类胎儿前脑烟碱受体亚基 mRNA 的选择性表达。

来自动物和人类研究的越来越多的证据表明,在发育过程中接触尼古丁,与吸烟的影响不同,会导致大脑发育失调,包括行为缺陷。人类胎儿大脑皮层的 RNAseq 研究表明,人类烟碱乙酰胆碱 (ACh) 受体亚基的 16 个基因中有 9 个在受孕后 7.5 至 12 周 (PCW) 之间选择性表达。表达最高的亚基基因是CHNRA4CHNRB2,其蛋白质产物结合形成在成人大脑中表达的最普遍的功能受体异构体。它们在 RNAseq 样本和组织切片中均表现出相关的表达原位杂交。与其他皮质标记的共定位研究表明,它们主要由皮质板和前亚板中的有丝分裂后谷氨酸能神经元前体表达,而不是皮质祖细胞或 GABA 能中间神经元前体。然而,神经节隆起中的 GABAergic 中间神经元祖细胞确实表达这些亚单位。CHNRA5也显示出中等水平的表达,并再次偏爱有丝分裂后的神经元。其他亚基,例如,CHRNA7,表现出低但可检测的表达水平。中华网发现不表达的基因包括通常被认为是肌肉特异性的亚基基因,例如,CHNRA1,尽管检测到一些肌肉特异性基因表达,例如CHNRB1. 尽管内在皮质神经元很少或根本没有合成乙酰胆碱,但来自基底前脑的胆碱能纤维最迟从 12 个 PCW 开始支配大脑皮层。乙酰胆碱可能对径向迁移的皮层神经元和 GABA 能中间神经元祖细胞具有旁分泌作用。

更新日期:2020-04-14
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