4.6 Article

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

Journal

BEHAVIOURAL BRAIN RESEARCH
Volume 214, Issue 2, Pages 187-192

Publisher

ELSEVIER
DOI: 10.1016/j.bbr.2010.05.016

Keywords

Depression; Anxiety; Hypothyroidism; Thyroid receptor alpha 1; Mice

Funding

  1. Faculty of Medicine, Charite Berlin

Ask authors/readers for more resources

Clinical evidence indicates that hypothyroidism contributes to mood disorders. The present study tested if the mutant thyroid hormone receptor alpha 1 (TR alpha 1) that causes a receptor-mediated hypothyroidism in the brain affects depressive and anxious behaviour in mice. Mice heterozygous for the TR alpha 1 allele (TR alpha 1 +/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 TR alpha 1 +/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. (C) 2010 Elsevier B.V. All rights reserved.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available