Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

<h4>Background</h4>Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone...

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Autores principales:	Soledad Bárez-López, Daniel Bosch-García, David Gómez-Andrés, Irene Pulido-Valdeolivas, Ana Montero-Pedrazuela, Maria Jesus Obregon, Ana Guadaño-Ferraz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/04265b4b1eda428496833123af502faa
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spelling	oai:doaj.org-article:04265b4b1eda428496833123af502faa2021-11-25T06:06:25ZAbnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.1932-620310.1371/journal.pone.0103857https://doaj.org/article/04265b4b1eda428496833123af502faa2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25083788/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone) in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO) did not find gross neurological alterations, possibly due to compensatory mechanisms.<h4>Aim</h4>This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed.<h4>Results</h4>Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice). No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction) and skeletal muscle (33% reduction), but not in the cerebellum where other deiodinase (type 1) is expressed.<h4>Conclusions</h4>The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.Soledad Bárez-LópezDaniel Bosch-GarcíaDavid Gómez-AndrésIrene Pulido-ValdeolivasAna Montero-PedrazuelaMaria Jesus ObregonAna Guadaño-FerrazPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e103857 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Soledad Bárez-López Daniel Bosch-García David Gómez-Andrés Irene Pulido-Valdeolivas Ana Montero-Pedrazuela Maria Jesus Obregon Ana Guadaño-Ferraz Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
description	<h4>Background</h4>Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3'-triiodothyronine (T3; the transcriptionally active hormone) in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO) did not find gross neurological alterations, possibly due to compensatory mechanisms.<h4>Aim</h4>This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed.<h4>Results</h4>Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice). No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction) and skeletal muscle (33% reduction), but not in the cerebellum where other deiodinase (type 1) is expressed.<h4>Conclusions</h4>The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders.
format	article
author	Soledad Bárez-López Daniel Bosch-García David Gómez-Andrés Irene Pulido-Valdeolivas Ana Montero-Pedrazuela Maria Jesus Obregon Ana Guadaño-Ferraz
author_facet	Soledad Bárez-López Daniel Bosch-García David Gómez-Andrés Irene Pulido-Valdeolivas Ana Montero-Pedrazuela Maria Jesus Obregon Ana Guadaño-Ferraz
author_sort	Soledad Bárez-López
title	Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
title_short	Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
title_full	Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
title_fullStr	Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
title_full_unstemmed	Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
title_sort	abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/04265b4b1eda428496833123af502faa
work_keys_str_mv	AT soledadbarezlopez abnormalmotorphenotypeatadultstagesinmicelackingtype2deiodinase AT danielboschgarcia abnormalmotorphenotypeatadultstagesinmicelackingtype2deiodinase AT davidgomezandres abnormalmotorphenotypeatadultstagesinmicelackingtype2deiodinase AT irenepulidovaldeolivas abnormalmotorphenotypeatadultstagesinmicelackingtype2deiodinase AT anamonteropedrazuela abnormalmotorphenotypeatadultstagesinmicelackingtype2deiodinase AT mariajesusobregon abnormalmotorphenotypeatadultstagesinmicelackingtype2deiodinase AT anaguadanoferraz abnormalmotorphenotypeatadultstagesinmicelackingtype2deiodinase
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Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase.

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