2024-03-28T16:29:05Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1244172022-12-15T10:51:13Zcom_10261_22com_10261_1col_10261_275
Abnormal motor phenotype at adult stages in mice lacking type 2 deiodinase
Bárez-López, Soledad
Bosch-García, Daniel
Gómez-Andrés, David
Pulido-Valdeolivas, Irene
Montero-Pedrazuela, Ana
Obregón, María Jesús
Guadaño-Ferraz, Ana
Ministerio de Ciencia e Innovación (España)
Ministerio de Economía y Competitividad (España)
Comunidad de Madrid
[Background]: 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. [Aim]: 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. [Results]: 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. [Conclusions]: 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.
This work was supported by grants from Plan Nacional de I+D: BFU2007-62979 and BFU 2010-16498 and SAF2011-25608 (AGF); SAF2012-32491 (MJO), Community of Madrid: S2010-BMD-2423 (MJO). SBL and DBG were recipients of a fellowship from the FPI program and AMP of a contract all from the Ministry of Science and Innovation and Economy and Competitiveness, Spain.
Peer Reviewed
2015-11-04T09:33:50Z
2015-11-04T09:33:50Z
2014
2015-11-04T09:33:50Z
artículo
http://purl.org/coar/resource_type/c_6501
doi: 10.1371/journal.pone.0103857
issn: 1932-6203
PLoS ONE 9(8): e103857 (2014)
http://hdl.handle.net/10261/124417
10.1371/journal.pone.0103857
http://dx.doi.org/10.13039/501100004837
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/100012818
25083788
#PLACEHOLDER_PARENT_METADATA_VALUE#
S2010/BMD-2423/MOIR
Publisher's version
http://dx.doi.org/10.1371/journal.pone.0103857
Sí
open
Public Library of Science