Thyroid hormone receptor alpha plays an essential role in the normalisation of adult-onset hypothyroidism-related hypoexpression of synaptic plasticity target genes in striatum

Autor: Paul Higueret, Olivier Chassande, V Enderlin, Julie Vallortigara
Přispěvatelé: PERIGNON, Alain, Unité de Nutrition et Neurosciences, Biomateriaux et Reparation Tissulaire, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)
Rok vydání: 2008
Předmět:
Endocrinology
Diabetes and Metabolism
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
[SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
Striatum
MESH: Mice
Knockout
MESH: Hypothyroidism
MESH: Corpus Striatum
Mice
Endocrinology
MESH: Thyroid Hormone Receptors beta
MESH: Animals
Neurogranin
MESH: Neuronal Plasticity
TRIIODOTHYRONINE NUCLEAR RECEPTORS
Mice
Knockout
Triiodothyronine
Neuronal Plasticity
STRIATUM
[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior
[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Thyroid Hormone Receptors beta
MESH: Gene Expression Regulation
medicine.anatomical_structure
Thyroid hormone receptor alpha
ADULT-ONSET HYPOTHYROIDISM
Thyroid function
hormones
hormone substitutes
and hormone antagonists
Thyroid Hormone Receptors alpha
medicine.medical_specialty
Thyroid Hormones
Central nervous system
MESH: Thyroid Hormone Receptors alpha
Biology
Cellular and Molecular Neuroscience
Hypothyroidism
MESH: Thyroid Hormones
Internal medicine
medicine
Animals
Humans
MUTANT MICE
MESH: Mice
MESH: Humans
Endocrine and Autonomic Systems
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
SYNAPTIC PLASTICITY-RELATED GENES
Corpus Striatum
Nuclear receptor
Gene Expression Regulation
Synaptic plasticity
[SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences
Zdroj: Journal of Neuroendocrinology
Journal of Neuroendocrinology, Wiley, 2009, 21 (1), pp.49-56. ⟨10.1111/j.1365-2826.2008.01802.x⟩
ISSN: 1365-2826
0953-8194
DOI: 10.1111/j.1365-2826.2008.01802.x⟩
Popis: Thyroid hormones (TH), particularly thyroxine (T4) and triiodothyro-nine (3,5,3¢-triiodothyronine, T3), are known to have pleiotrophiceffects in various tissues, including brain, liver, heart, kidney, lung,bone and adipose tissue. The brain is an important target for TH.TH deficiency during the foetal and postnatal periods in humansmay cause irreversible mental retardation, as seen in cretinism, aswell as neurological and behavioural deficits, and long-lasting irre-versible motor dysfunctions (1, 2). In addition to this well-known,essential role of TH during the normal development of the centralnervous system, some studies suggest that thyroid function abnor-malities in adulthood may also have profound behavioural conse-quences, such as anxiety, depressive symptoms and impairedmemory (3, 4).The main active compound at the genomic level is T3, which isessentially formed in extrathyroidal tissues from T4 after deiodin-ation (5). T3 action is mediated by specific nuclear receptors (TR),functioning as ligand-dependent transcription factors to increase ordecrease the expression of target genes. There are two TR genes:TRa and TRb, which encode nine proteins, generated by alternativesplicing and differential promoter usage. Among these, only fourreceptor isoforms (TRa1, TRb1, TRb2 and TRb3) have intact DNAand hormone-binding domains (1). The role of the nonreceptor iso-forms (TRa2, TRa3, DTRa1, DTRa2 and DTRb3) is still unclear (6). Inadult rodent brains, TRa1 accounts for a large fraction of all TRreceptors in the brain, whereas TRb transcripts (b1 and b2) aredetected in few areas (7–9). Among T3 target genes in the brain,some code for TRs and others for neurogranin (RC3 or Nrgn) andRas homologue enriched in striatum (Rhes or Rasd2). These proteinsare co-expressed in the main striatal neurones, medium-sizedspiny cells, where they show a strong dependence on TH (10–12).
Databáze: OpenAIRE
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