Thyroid hormone receptor alpha plays an essential role in the normalisation of adult-onset hypothyroidism-related hypoexpression of synaptic plasticity target genes in striatum.
Thyroid hormone (TH) deficiency leads to molecular changes resulting in behavioural deficits. TH action is mediated by two types of nuclear receptors (TRs), TRalpha and TRbeta, which control target gene transcription. The relative contributions of the two TR products in mediating adult TH responses are poorly understood. As TRalpha1 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 (TRalpha1, TRbeta) and synaptic plasticity gene expression in TRalpha(0/0), TRbeta(-/-) and wild-type 129/SV mice. Hypothyroid wild-type mice exhibited reduced TRbeta, RC3, CaMKII and Rhes expression. The mRNA levels of Rhes and CaMKII were the same in all three hypothyroid substrains. By contrast, hypothyroid TRbeta(-/-) mice had higher RC3 mRNA levels than wild-type. T3 administration restored TRbeta, RC3 and CaMKII levels in hypothyroid wild-type mice, without significant Rhes upregulation. T3 administration normalised expression of all genes studied in hypothyroid TRbeta(-/-) but not TRalpha(0/0) mice. Thus, TRalpha apparently plays an essential role in restoring the expression of the TH-regulated genes potentially involved in striatal synaptic plasticity.
Vallortigara
J
J
Unité de Nutrition et Neurosciences, Universités Bordeaux 1-Bordeaux 2, Avenue des Facultés, Talence, France.
Chassande
O
O
Higueret
P
P
Enderlin
V
V
D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics*; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D037042:Thyroid Hormone Receptors beta / Q000235:genetics / Q000378:metabolism; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism
D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones