Bárez-López Soledad, Guadaño-Ferraz Ana
Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC), Universidad Autónoma de Madrid (UAM)Madrid, Spain.
Center for Biomedical Research on Rare Diseases (Ciberer), Instituto de Salud Carlos IIIMadrid, Spain.
Front Cell Neurosci. 2017 Aug 14;11:240. doi: 10.3389/fncel.2017.00240. eCollection 2017.
Thyroid hormones (THs) play an essential role in the development of all vertebrates; in particular adequate TH content is crucial for proper neurodevelopment. TH availability and action in the brain are precisely regulated by several mechanisms, including the secretion of THs by the thyroid gland, the transport of THs to the brain and neural cells, THs activation and inactivation by the metabolic enzymes deiodinases and, in the fetus, transplacental passage of maternal THs. Although these mechanisms have been extensively studied in rats, in the last decade, models of genetically modified mice have been more frequently used to understand the role of the main proteins involved in TH signaling in health and disease. Despite this, there is little knowledge about the mechanisms underlying THs availability in the mouse brain. This mini-review article gathers information from findings in rats, and the latest findings in mice regarding the ontogeny of TH action and the sources of THs to the brain, with special focus on neurodevelopmental stages. Unraveling TH economy and action in the mouse brain may help to better understand the physiology and pathophysiology of TH signaling in brain and may contribute to addressing the neurological alterations due to hypo and hyperthyroidism and TH resistance syndromes.
甲状腺激素(THs)在所有脊椎动物的发育过程中起着至关重要的作用;特别是充足的TH含量对于正常的神经发育至关重要。大脑中TH的可用性和作用受到多种机制的精确调节,包括甲状腺分泌TH、TH向大脑和神经细胞的转运、代谢酶脱碘酶对TH的激活和失活,以及在胎儿期母体TH的胎盘转运。尽管这些机制已在大鼠中得到广泛研究,但在过去十年中,基因改造小鼠模型被更频繁地用于了解参与TH信号传导的主要蛋白质在健康和疾病中的作用。尽管如此,关于小鼠大脑中TH可用性的潜在机制仍知之甚少。这篇小型综述文章收集了大鼠研究结果以及小鼠关于TH作用的个体发生和大脑TH来源的最新研究结果,特别关注神经发育阶段。阐明小鼠大脑中的TH代谢和作用可能有助于更好地理解大脑中TH信号传导的生理学和病理生理学,并可能有助于解决由于甲状腺功能减退和亢进以及TH抵抗综合征引起的神经改变。