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T3 administration in adult hypothyroid mice modulates expression of proteins involved in striatal synaptic plasticity and improves motor behavior

Abstract : Adult-onset hypothyroidism is associated with neurological changes such as cognitive dysfunction and impaired learning, which may be related to alterations of synaptic plasticity. We investigate the consequence of adult-onset hypothyroidism on thyroid-mediated transcription events in striatal synaptic plasticity, and the effect of triiodothyronine (T3) replacement. We used hypothyroid mice, treated with propylthiouracil (PTU) and methimazole (MMI), with or without subsequent administration of T3. We evaluated the amount of T3 nuclear receptors (TRalpha1, TRbeta) and striatal plasticity indicators: neurogranin (RC3), Ras homolog enriched in striatum (Rhes), Ca2+/calmodulin-dependent protein kinase (CaMKII), and dopamine- and cAMP-regulated phosphoprotein (DARPP-32). In addition, we assessed hypothyroid mice motor behavior as related to striatum synaptic functions. Hypothyroid mice exhibited significantly reduced TRbeta, RC3 and Rhes expression. T3 administration reversed the expression of TRbeta, RC3, and up-regulated CaMKII levels as well as motor behavior, and decreased DARPP-32 protein phosphorylation. We suggest that thyroid hormone modulation had a major impact on striatal synaptic plasticity of adult mice which produced in turn motor behavior modifications.
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https://hal-cnrs.archives-ouvertes.fr/hal-02526780
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Submitted on : Tuesday, March 31, 2020 - 5:45:24 PM
Last modification on : Saturday, May 30, 2020 - 12:15:26 AM

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Julie Vallortigara, Serge Alfos, Jacques Micheau, Paul Higueret, Valérie Enderlin. T3 administration in adult hypothyroid mice modulates expression of proteins involved in striatal synaptic plasticity and improves motor behavior. Neurobiology of Disease, Elsevier, 2008, 31 (3), pp.378-385. ⟨10.1016/j.nbd.2008.05.015⟩. ⟨hal-02526780⟩

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