Increased depressive behaviour in mice harboring the mutant thyroid hormone receptor alpha 1.

Abstract

Clinical evidence indicates that hypothyroidism contributes to mood disorders. The present study tested if the mutant thyroid hormone receptor alpha 1 (TRalpha1) that causes a receptor-mediated hypothyroidism in the brain affects depressive and anxious behaviour in mice. Mice heterozygous for the TRalpha1 allele (TRalpha1+/m), yielding a receptor protein with a 10-fold reduced affinity to triiodothyronine (T3), and wildtype (wt) mice were subjected to several paradigms specifically testing depressive and anxious behaviour. Mutant and wt mice were either treated with T3 or vehicle. Untreated TRalpha1+/m animals displayed reduced locomotion, higher rates of helplessness in the shuttle box-, greater levels of anxiety in the startle response- and dark light box behavioural paradigms when compared to wt mice. Continuous T3-substitution therapy was effective in alleviating anxious and depressive behaviour without affecting locomotion in mutant mice. Notably, continuous T3-substitution reduced overall locomotion and increased helpless behaviour in wt mice when compared to untreated wt mice. The data suggest that receptor-mediated hypothyroidism caused by an unliganded thyroid hormone receptor alpha 1 leads to a depressive and anxious phenotype in mice, which is responsive to continuous T3-substitution and that an iatrogeneously induced hyperthyreoidism by continuous T3-administration leads to a hypolocomotive and depressive phenotype.

• Authors: Maximilian Pilhatsch, Christine Winter, Kristina Nordström, Björn Vennström, Michael Bauer, Georg Juckel
• Journal: Behavioural brain research (Behav Brain Res) Vol. 214 Issue 2 Pg. 187-92 (Dec 25 2010) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 20580649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• Thyroid Hormone Receptors alpha
• Triiodothyronine

Topics

• Animals
• Anxiety (drug therapy, genetics)
• Behavior, Animal (drug effects)
• Depression (drug therapy, genetics)
• Disease Models, Animal
• Female
• Heterozygote
• Hormone Replacement Therapy (psychology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Thyroid Hormone Receptors alpha (genetics)
• Triiodothyronine (therapeutic use)