Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development

Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to profound brain alterations, including myelination impairments, in humans. We aimed to further explore the pathophysiological mechanisms underlying the MCT8 deficiency-associated myelination impairments to unrav...

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Autores principales:	Víctor Valcárcel-Hernández, Daniela López-Espíndola, Marina Guillén-Yunta, Ángel García-Aldea, Inés López de Toledo Soler, Soledad Bárez-López, Ana Guadaño-Ferraz
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	MCT8 deficiency Human brain Myelin Mouse model Oligodendroglia Thyroid hormones Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/589a1f6799c14691a43c1635754f92f2
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spelling	oai:doaj.org-article:589a1f6799c14691a43c1635754f92f22021-11-30T04:13:41ZDeficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development1095-953X10.1016/j.nbd.2021.105567https://doaj.org/article/589a1f6799c14691a43c1635754f92f22022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0969996121003168https://doaj.org/toc/1095-953XMutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to profound brain alterations, including myelination impairments, in humans. We aimed to further explore the pathophysiological mechanisms underlying the MCT8 deficiency-associated myelination impairments to unravel new biomarkers and therapeutic targets. We have performed brain histological analysis on an MCT8-deficient subject and histological, ultrastructural, and magnetic resonance imaging (MRI) analysis in the brain of a mouse model of the syndrome, lacking MCT8 and enzyme deiodinase type 2 (DIO2, Mct8/Dio2 KO). We have found that the MCT8-deficient subject presents severely reduced myelin lipid and protein staining and increased proportion of small-caliber myelinated axons in detriment of large-caliber ones. Mct8/Dio2 KO mice present myelination impairments and abnormal oligodendroglial development. We conclude that the greater proportion of small-caliber axons and impairments in the oligodendroglia lineage progression arise as potential mechanisms underlying the permanent myelination defects in MCT8-deficiency. Moreover, we present the Mct8/Dio2 KO mouse model, and MRI as a non-invasive biomarker, as highly valuable tools for preclinical studies involving MCT8 deficiency. These findings contribute to the understanding of the pathological mechanisms in MCT8 deficiency and suggest new biomarkers and therapeutic targets to consider therapeutic options for the neurological defects in patients.Víctor Valcárcel-HernándezDaniela López-EspíndolaMarina Guillén-YuntaÁngel García-AldeaInés López de Toledo SolerSoledad Bárez-LópezAna Guadaño-FerrazElsevierarticleMCT8 deficiencyHuman brainMyelinMouse modelOligodendrogliaThyroid hormonesNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Disease, Vol 162, Iss , Pp 105567- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	MCT8 deficiency Human brain Myelin Mouse model Oligodendroglia Thyroid hormones Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	MCT8 deficiency Human brain Myelin Mouse model Oligodendroglia Thyroid hormones Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Víctor Valcárcel-Hernández Daniela López-Espíndola Marina Guillén-Yunta Ángel García-Aldea Inés López de Toledo Soler Soledad Bárez-López Ana Guadaño-Ferraz Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development
description	Mutations in the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) lead to profound brain alterations, including myelination impairments, in humans. We aimed to further explore the pathophysiological mechanisms underlying the MCT8 deficiency-associated myelination impairments to unravel new biomarkers and therapeutic targets. We have performed brain histological analysis on an MCT8-deficient subject and histological, ultrastructural, and magnetic resonance imaging (MRI) analysis in the brain of a mouse model of the syndrome, lacking MCT8 and enzyme deiodinase type 2 (DIO2, Mct8/Dio2 KO). We have found that the MCT8-deficient subject presents severely reduced myelin lipid and protein staining and increased proportion of small-caliber myelinated axons in detriment of large-caliber ones. Mct8/Dio2 KO mice present myelination impairments and abnormal oligodendroglial development. We conclude that the greater proportion of small-caliber axons and impairments in the oligodendroglia lineage progression arise as potential mechanisms underlying the permanent myelination defects in MCT8-deficiency. Moreover, we present the Mct8/Dio2 KO mouse model, and MRI as a non-invasive biomarker, as highly valuable tools for preclinical studies involving MCT8 deficiency. These findings contribute to the understanding of the pathological mechanisms in MCT8 deficiency and suggest new biomarkers and therapeutic targets to consider therapeutic options for the neurological defects in patients.
format	article
author	Víctor Valcárcel-Hernández Daniela López-Espíndola Marina Guillén-Yunta Ángel García-Aldea Inés López de Toledo Soler Soledad Bárez-López Ana Guadaño-Ferraz
author_facet	Víctor Valcárcel-Hernández Daniela López-Espíndola Marina Guillén-Yunta Ángel García-Aldea Inés López de Toledo Soler Soledad Bárez-López Ana Guadaño-Ferraz
author_sort	Víctor Valcárcel-Hernández
title	Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development
title_short	Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development
title_full	Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development
title_fullStr	Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development
title_full_unstemmed	Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development
title_sort	deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/589a1f6799c14691a43c1635754f92f2
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Deficient thyroid hormone transport to the brain leads to impairments in axonal caliber and oligodendroglial development

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