甲状腺激素转运体在出生后小鼠大脑中的表达模式。

Expression pattern of thyroid hormone transporters in the postnatal mouse brain.

机构信息

Leibniz Institute for Age Research - Fritz Lipmann Institute , Jena , Germany.

Leibniz Institute for Age Research - Fritz Lipmann Institute , Jena , Germany ; Leibniz Research Institute for Environmental Medicine , Düsseldorf , Germany.

出版信息

Front Endocrinol (Lausanne). 2014 Jun 18;5:92. doi: 10.3389/fendo.2014.00092. eCollection 2014.

Abstract

For a comprehensive description of the tissue-specific thyroidal state under normal as well as under pathophysiological conditions it is of utmost importance to include thyroid hormone (TH) transporters in the analysis as well. The current knowledge of the cell-specific repertoire of TH transporters, however, is still rather limited, although several TH transporting proteins have been identified. Here, we describe the temporal and spatial distribution pattern of the most prominent TH transporters in the postnatal mouse brain. For that purpose, we performed radioactive in situ hybridization studies in order to analyze the cellular mRNA expression pattern of the monocarboxylate transporters Mct8 and Mct10, the L-type amino acid transporters Lat1 and Lat2 as well as the organic anion transporting peptide Oatp1c1 at different postnatal time points. Highest TH transporter expression levels in the CNS were observed at postnatal day 6 and 12, while hybridization signal intensities visibly declined after the second postnatal week. The only exception was Mct10 for which the strongest signals could be observed in white matter regions at postnatal day 21 indicating that this transporter is preferentially expressed in mature oligodendrocytes. Whereas Mct8 and Lat2 showed an overlapping neuronal mRNA expression pattern in the cerebral cortex, hippocampus, and in the hypothalamus, Oatp1c1 and Lat1 specific signals were most prominent in capillary endothelial cells throughout the CNS. In the choroid plexus, expression of three transporters (Mct8, Lat2, and Oatp1c1) could be detected, whereas in other brain areas (e.g., striatum, thalamus, and brain stem nuclei) only one of the transporter candidates appeared to be present. Overall, our study revealed a distinct mRNA distribution pattern for each of the TH transporter candidates. Further studies will reveal to which extent these transporters contribute to the cell-specific TH uptake and efflux in the mouse CNS.

摘要

为了全面描述正常和病理生理条件下组织特异性甲状腺状态,分析甲状腺激素(TH)转运蛋白至关重要。然而,尽管已经鉴定出几种 TH 转运蛋白,但对细胞特异性 TH 转运蛋白的认识仍然相当有限。在这里,我们描述了在新生小鼠大脑中最突出的 TH 转运蛋白的时空分布模式。为此,我们进行了放射性原位杂交研究,以分析单羧酸转运蛋白 Mct8 和 Mct10、L 型氨基酸转运蛋白 Lat1 和 Lat2 以及有机阴离子转运肽 Oatp1c1 的细胞 mRNA 表达模式在不同的出生后时间点。中枢神经系统中最高的 TH 转运蛋白表达水平出现在出生后第 6 天和第 12 天,而在第二周后,杂交信号强度明显下降。唯一的例外是 Mct10,其最强的信号可以在出生后第 21 天的白质区域观察到,这表明该转运蛋白优先在成熟的少突胶质细胞中表达。虽然 Mct8 和 Lat2 在大脑皮层、海马体和下丘脑表现出重叠的神经元 mRNA 表达模式,但 Oatp1c1 和 Lat1 的特异性信号在整个中枢神经系统的毛细血管内皮细胞中最为突出。在脉络丛中,可以检测到三种转运蛋白(Mct8、Lat2 和 Oatp1c1)的表达,而在其他脑区(例如纹状体、丘脑和脑干核),似乎只有一种转运蛋白候选物存在。总的来说,我们的研究揭示了每种 TH 转运蛋白候选物的独特 mRNA 分布模式。进一步的研究将揭示这些转运蛋白在多大程度上有助于小鼠中枢神经系统中细胞特异性 TH 摄取和外排。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/22d1/4061481/b58fb0672a0e/fendo-05-00092-g001.jpg

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