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Thyroid Hormone Receptor Alpha Plays an Essential Role in the Normalisation of Adult‐Onset Hypothyroidism‐Related Hypoexpression of Synaptic Plasticity Target Genes in Striatum
Author(s) -
Vallortigara J.,
Chassande O.,
Higueret P.,
Enderlin V.
Publication year - 2009
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.2008.01802.x
Subject(s) - endocrinology , medicine , striatum , nuclear receptor , biology , receptor , synaptic plasticity , wild type , gene expression , downregulation and upregulation , gene , transcription factor , mutant , dopamine , genetics
Thyroid hormone (TH) deficiency leads to molecular changes resulting in behavioural deficits. TH action is mediated by two types of nuclear receptors (TRs), TRα and TRβ, which control target gene transcription. The relative contributions of the two TR products in mediating adult TH responses are poorly understood. As TRα1 transcripts are widely distributed in the brain, they presumably mediate most of the TH effects. This report examines the role and specific functions of T3 receptor isoforms on regulation of striatal synaptic plasticity indicators using adult hypothyroid mutant mice that fail to express single or multiple TR gene products. We then evaluated the effect of this hypothyroidism, with or without subsequent administration of T3, on T3 nuclear receptor (TRα1, TRβ) and synaptic plasticity gene expression in TRα 0/0 , TRβ −/− and wild‐type 129/SV mice. Hypothyroid wild‐type mice exhibited reduced TRβ, RC3, CaMKII and Rhes expression. The mRNA levels of Rhes and CaMKII were the same in all three hypothyroid substrains. By contrast, hypothyroid TRβ −/− mice had higher RC3 mRNA levels than wild‐type. T3 administration restored TRβ, RC3 and CaMKII levels in hypothyroid wild‐type mice, without significant Rhes upregulation. T3 administration normalised expression of all genes studied in hypothyroid TRβ −/− but not TRα 0/0 mice. Thus, TRα apparently plays an essential role in restoring the expression of the TH‐regulated genes potentially involved in striatal synaptic plasticity.