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Cadaverine and Spermine Elicit Ca2+ Uptake in Human CP Cells via a Trace Amine-Associated Receptor 1 Dependent Pathway.
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2020-08-20 , DOI: 10.1007/s12031-020-01684-8
D Almeida-Santos 1 , A C Duarte 1 , I Gonçalves 1 , Catarina L Ferreira 1 , I Ferrer 2, 3 , Hiroshi Ishikawa 4 , Christian Schwerk 5 , Horst Schroten 5 , Cecília R A Santos 1
Affiliation  

The choroid plexus (CP) constitutes a barrier between the blood and the cerebrospinal fluid (CSF) which regulates the exchange of substances between these two fluids through mechanisms that are not completely understood. Polyamines as spermine, spermidine and putrescine are produced by all cells and are present in the CSF. Interestingly, their levels are altered in some neuronal disorders as Alzheimer’s and Parkinson’s diseases, thus increasing the interest in their signalling in the central nervous system (CNS). Cadaverine, on the other hand, is synthetized by the intestinal microbiome, suggesting that the presence of this bacterial metabolite in the CSF requires that it is up taken to the CNS across brain barriers. We knew that polyamines are detected by the olfactory signalling cascade operating at the CP, but the receptor involved had not been identified. The zebrafish TAAR13c was the only receptor known to bind a polyamine-cadaverine. Thus, we searched for a human receptor with homology to TAAR13c and found that some human TAARs including TAAR1 showed great homology. Then, we confirmed the expression of TAAR1 mRNA and protein in a human cell line of the CP, and in human CP samples. Calcium imaging assays after TAAR1 knockdown in these cells with a specific siRNA against TAAR1 showed a consistent reduction in the responses of these cells to cadaverine and spermidine, but not to spermine, suggesting that TAAR1 is activated by cadaverine and spermidine, but not spermine.



中文翻译:

尸胺和精胺通过微量胺相关受体 1 依赖性途径诱导人 CP 细胞摄取 Ca2+。

脉络丛 (CP) 构成了血液和脑脊液 (CSF) 之间的屏障,它通过尚未完全了解的机制调节这两种流体之间的物质交换。多胺如精胺、亚精胺和腐胺由所有细胞产生并存在于脑脊液中。有趣的是,在某些神经元疾病(如阿尔茨海默病和帕金森病)中,它们的水平会发生改变,从而增加了对它们在中枢神经系统 (CNS) 中信号传导的兴趣。另一方面,尸胺是由肠道微生物组合成的,这表明脑脊液中这种细菌代谢物的存在需要它穿过脑屏障进入中枢神经系统。我们知道多胺是通过在 CP 上运行的嗅觉信号级联检测到的,但所涉及的受体尚未确定。斑马鱼 TAAR13c 是唯一已知的与多胺-尸胺结合的受体。因此,我们搜索了一种与 TAAR13c 具有同源性的人类受体,发现包括 TAAR1 在内的一些人类 TAARs 表现出很大的同源性。然后,我们确认了 TAAR1 mRNA 和蛋白质在 CP 的人类细胞系和人类 CP 样品中的表达。在这些细胞中用针对 TAAR1 的特定 siRNA 敲低 TAAR1 后的钙成像分析显示,这些细胞对尸胺和亚精胺的反应持续降低,但对精胺没有,这表明 TAAR1 被尸胺和亚精胺激活,但不是精胺。我们搜索了一种与 TAAR13c 具有同源性的人类受体,发现包括 TAAR1 在内的一些人类 TAARs 表现出很大的同源性。然后,我们确认了 TAAR1 mRNA 和蛋白质在 CP 的人类细胞系和人类 CP 样品中的表达。在这些细胞中用针对 TAAR1 的特定 siRNA 敲低 TAAR1 后的钙成像分析显示,这些细胞对尸胺和亚精胺的反应持续降低,但对精胺没有,这表明 TAAR1 被尸胺和亚精胺激活,但不是精胺。我们搜索了一种与 TAAR13c 具有同源性的人类受体,发现包括 TAAR1 在内的一些人类 TAARs 表现出很大的同源性。然后,我们确认了 TAAR1 mRNA 和蛋白质在 CP 的人类细胞系和人类 CP 样品中的表达。在这些细胞中用针对 TAAR1 的特定 siRNA 敲低 TAAR1 后的钙成像分析显示,这些细胞对尸胺和亚精胺的反应持续降低,但对精胺没有,这表明 TAAR1 被尸胺和亚精胺激活,但不是精胺。

更新日期:2020-08-20
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