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01-07-2019 | Original Article

Thyroid hormone availability in the human fetal brain: novel entry pathways and role of radial glia

Authors: Daniela López-Espíndola, Ángel García-Aldea, Inés Gómez de la Riva, Ana Margarita Rodríguez-García, Domenico Salvatore, Theo J. Visser, Juan Bernal, Ana Guadaño-Ferraz

Published in: Brain Structure and Function | Issue 6/2019

Abstract

Thyroid hormones (TH) are crucial for brain development; their deficiency during neurodevelopment impairs neural cell differentiation and causes irreversible neurological alterations. Understanding TH action, and in particular the mechanisms regulating TH availability in the prenatal human brain is essential to design therapeutic strategies for neurological diseases due to impaired TH signaling during neurodevelopment. We aimed at the identification of cells involved in the regulation of TH availability in the human brain at fetal stages. To this end, we studied the distribution of the TH transporters monocarboxylate transporter 8 (MCT8) and organic anion-transporting polypeptide 1C1 (OATP1C1), as well as the TH-metabolizing enzymes types 2 and 3 deiodinases (DIO2 and DIO3). Paraffin-embedded human brain sections obtained from necropsies of thirteen fetuses from 14 to 38 gestational weeks were analyzed by immunohistochemistry and in situ hybridization. We found these proteins localized along radial glial cells, in brain barriers, in Cajal-Retzius cells, in migrating fibers of the brainstem and in some neurons and glial cells with particular and complex spatiotemporal patterns. Our findings point to an important role of radial glia in controlling TH delivery and metabolism and suggest two additional novel pathways for TH availability in the prenatal human brain: the outer, and the inner cerebrospinal fluid–brain barriers. Based on our data we propose a model of TH availability for neural cells in the human prenatal brain in which several cell types have the ability to autonomously control the required TH content.

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Title: Thyroid hormone availability in the human fetal brain: novel entry pathways and role of radial glia
Authors: Daniela López-Espíndola
Ángel García-Aldea
Inés Gómez de la Riva
Ana Margarita Rodríguez-García
Domenico Salvatore
Theo J. Visser
Juan Bernal
Ana Guadaño-Ferraz
Publication date: 01-07-2019
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 6/2019
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-019-01896-8

At a glance: The STEP trials

Springer Medicine

Thyroid hormone availability in the human fetal brain: novel entry pathways and role of radial glia

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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