| 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. |
| Authors | Julie Vallortigara, Serge Alfos, Jacques Micheau, Paul Higueret, Valérie Enderlin
(Affiliation: Unité de Nutrition et Neurosciences, Universités Bordeaux 1-Bordeaux 2, Avenue des Facultés, 33405 Talence Cedex, France.)
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| Journal | Neurobiology of disease
(Neurobiol Dis)
Vol. 31
Issue 3
Pg. 378-85
(Sep 2008)
ISSN: 1095-953X United States |
| PMID | 18585460
(Publication Type: Journal Article)
|
| Chemical References |
- Biological Markers
- Dopamine and cAMP-Regulated Phosphoprotein 32
- Ppp1r1b protein, mouse
- Receptors, Thyroid Hormone
- Neurogranin
- Propylthiouracil
- Methimazole
- Triiodothyronine
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- GTP-Binding Proteins
- Rasd2 protein, mouse
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| Topics |
- Age Factors
- Animals
- Behavior, Animal
(drug effects, physiology)
- Biological Markers
(analysis, metabolism)
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
(drug effects, metabolism)
- Corpus Striatum
(drug effects, metabolism, physiopathology)
- Disease Models, Animal
- Dopamine and cAMP-Regulated Phosphoprotein 32
(drug effects, metabolism)
- GTP-Binding Proteins
(drug effects, metabolism)
- Hypothyroidism
(complications, drug therapy, metabolism)
- Male
- Methimazole
- Mice
- Motor Activity
(drug effects, physiology)
- Movement Disorders
(drug therapy, etiology, metabolism)
- Neurogranin
(drug effects, metabolism)
- Neuronal Plasticity
(drug effects)
- Phosphorylation
(drug effects)
- Presynaptic Terminals
(drug effects, metabolism)
- Propylthiouracil
- Receptors, Thyroid Hormone
(drug effects, metabolism)
- Synaptic Transmission
(drug effects, physiology)
- Thyroid Gland
(drug effects, metabolism, physiopathology)
- Triiodothyronine
(administration & dosage)
- Up-Regulation
(drug effects, physiology)
|
