Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency

© Mary Ann Liebert, Inc.

Detalles Bibliográficos
Autores: Grijota Martínez, María del Carmen, Montero-Pedrazuela, Ana, Hidalgo-Álvarez, Jorge, Bárez-López, Soledad, Guadaño-Ferraz, Ana
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/340350
Acceso en línea:http://hdl.handle.net/10261/340350
Access Level:acceso abierto
Palabra clave:Thyroid hormones
MCT8 deficiency
TRIAC
Intracerebroventricular
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network_name_str España
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dc.title.none.fl_str_mv Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
title Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
spellingShingle Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
Grijota Martínez, María del Carmen
Thyroid hormones
MCT8 deficiency
TRIAC
Intracerebroventricular
title_short Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
title_full Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
title_fullStr Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
title_full_unstemmed Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
title_sort Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 Deficiency
dc.creator.none.fl_str_mv Grijota Martínez, María del Carmen
Montero-Pedrazuela, Ana
Hidalgo-Álvarez, Jorge
Bárez-López, Soledad
Guadaño-Ferraz, Ana
author Grijota Martínez, María del Carmen
author_facet Grijota Martínez, María del Carmen
Montero-Pedrazuela, Ana
Hidalgo-Álvarez, Jorge
Bárez-López, Soledad
Guadaño-Ferraz, Ana
author_role author
author2 Montero-Pedrazuela, Ana
Hidalgo-Álvarez, Jorge
Bárez-López, Soledad
Guadaño-Ferraz, Ana
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Consejo Superior de Investigaciones Científicas (España)
Sherman Foundation
Agencia Estatal de Investigación (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Thyroid hormones
MCT8 deficiency
TRIAC
Intracerebroventricular
topic Thyroid hormones
MCT8 deficiency
TRIAC
Intracerebroventricular
description © Mary Ann Liebert, Inc.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/340350
url http://hdl.handle.net/10261/340350
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-86342-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113139RB-I00
info:eu-repo/grantAgreement/AEI//IJC2020-043543-I
http://dx.doi.org/10.1089/thy.2022.0562
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Mary Ann Liebert
publisher.none.fl_str_mv Mary Ann Liebert
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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spelling Intracerebroventricular High Doses of 3,3′,5-Triiodothyroacetic Acid at Juvenile Stages Improve Peripheral Hyperthyroidism and Mediate Thyromimetic Effects in Limited Brain Regions in a Mouse Model of Monocarboxylate Transporter 8 DeficiencyGrijota Martínez, María del CarmenMontero-Pedrazuela, AnaHidalgo-Álvarez, JorgeBárez-López, SoledadGuadaño-Ferraz, AnaThyroid hormonesMCT8 deficiencyTRIACIntracerebroventricular© Mary Ann Liebert, Inc.[Introduction]: Patients lacking functional monocarboxylate transporter 8 (MCT8), a highly specific thyroid hormone (TH) transporter, present severe psychomotor disabilities. MCT8 deficiency leads to peripheral hyperthyroidism and brain hypothyroidism, the latter due to impaired transport of TH across brain barriers. Available treatments for patients are limited and aim to overcome the limited TH transport across brain barriers. The use of TH analogues such as 3,3′,5-triiodothyroacetic acid (TRIAC) that do not require MCT8 to cross the cellular membranes is considered a potential therapy for MCT8 deficiency. Previous studies have shown that systemic administration of TRIAC at therapeutic doses does not increase TRIAC content in the brain, while intracerebroventricular (ICV) administration of therapeutic doses of TRIAC increases TRIAC content in the brain but does not mediate thyromimetic effects. In view of this, we hypothesize that ICV administration of high doses of TRIAC can mediate thyromimetic effects in the brain without worsening the brain hypothyroidism or peripheral hyperthyroidism of patients. [Methods]: We administered 400 ng/g of body weight per day of ICV TRIAC in a mouse model of MCT8 deficiency: Mct8−/y and deiodinase 2 (Dio2)−/− double knockout mice. The effects of this treatment on TH and TRIAC levels/content in blood and tissues were determined by radioimmunoassay and effects on TH-regulated genes were assessed by real time-quantitative polymerase chain reaction in peripheral and central tissues. [Results]: ICV administration of high doses of TRIAC ameliorated the peripheral hyperthyroidism. In the brain, this treatment did not further aggravate brain hypothyroidism and increased TRIAC content in several brain regions; however, only moderate thyromimetic activity was observed in restricted brain areas. [Conclusion]: Administration of high doses of TRIAC by ICV delivery at juvenile stages in a mouse model of MCT8 deficiency is effective in normalizing peripheral hyperthyroidism but exerts minimal thyromimetic activity in the brain.This research was supported by grants from the Ministerio de Ciencia e Innovacion (MCIN)/AEI/10.13039/501100011033 (Grant No. SAF2017-86342-R to A.G.-F.); MCIN/AEI/10.13039/501100011033/FEDER ‘‘Una manera de hacer Europa’’ (Grant No. PID2020-113139RB-I00 to A.G.-F.); Consejo Superior de Investigaciones Cientı´ficas (Grant No. 2020AEP044 to A.G.-F.); the Sherman Foundation (Grant No. OTR02211 to S.B.-L. and A.G.-F.); Asociacio´n Corriendo con el Corazo´n por Hugo (Grant No. OTR06190 to A.G.-F.); and MCIN/EU (Grant No. IJC2020-043543-I to S.B-L).Peer reviewedMary Ann LiebertMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Consejo Superior de Investigaciones Científicas (España)Sherman FoundationAgencia Estatal de Investigación (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2023202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/340350reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-86342-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-113139RB-I00info:eu-repo/grantAgreement/AEI//IJC2020-043543-Ihttp://dx.doi.org/10.1089/thy.2022.0562Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3403502026-05-22T06:33:51Z
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