Neuronal expression of a thyroid hormone receptor α mutation alters mouse behaviour

• Published in: Behavioural brain research 2017-03, Vol.321, p.18-27
• Main Authors: Richard, S., Aguilera, N., Thévenet, M., Dkhissi-Benyahya, O., Flamant, F.
• Format: Article
• Language: English
• Subjects: Animal model; Animals; Anxiety; Anxiety - metabolism; Anxiety - pathology; Behavior, Animal; Behavior, Animal - physiology; Brain; Brain - metabolism; Brain - pathology; Circadian Rhythm; Circadian Rhythm - physiology; Conditional gene targeting; Depression; Depression - metabolism; Depression - pathology; Development Biology; Female; Housing, Animal; Hypothyroidism; Hypothyroidism - metabolism; Hypothyroidism - psychology; Life Sciences; Male; Mice, Transgenic; Motor Activity; Motor Activity - physiology; Mutation; Neurons; Neurons - metabolism; Neurons - pathology; Stress, Psychological; Stress, Psychological - metabolism; Stress, Psychological - pathology; Thyroid Hormone Receptors alpha; Thyroid Hormone Receptors alpha - genetics; Thyroid Hormone Receptors alpha - metabolism; Thyroid Hormones; Thyroid Hormones - blood
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2016.12.025

•The role of central thyroid hormone receptors in emotional behaviour was assessed.•A neuron-specific TRα mutation induced anxiety-like behaviour in mice.•Stressful housing conditions potentiated the effects of the TRα mutation.•We conclude that neuronal TRα signalling influences adult anxiety behaviour.•Neuronal TRα thus constitutes a functional link between hypothyroidism and anxiety. In humans, alterations in thyroid hormone signalling are associated with mood and anxiety disorders, but the neural mechanisms underlying such association are poorly understood. The present study investigates the involvement of neuronal thyroid hormone receptor α (TRα) in anxiety, using mouse genetics and Cre/loxP technology to specifically alter TRα signalling in neurons. We evaluated the behaviour of mice expressing a dominant negative, neuron-specific mutation of TRα (TRαAMI/Cre3 mice), using the elevated-plus maze, light-dark box and open-field tests. In a first experiment, mice were housed individually, and the behaviour of TRαAMI/Cre3 mice differed significantly from that of control littermates in these 3 tests, suggesting heightened anxiety. In a second experiment, designed to evaluate the robustness of the results with the same 3 tests, mice were housed in groups. In these conditions, the behaviour of TRαAMI/Cre3 mice differed from that of control littermates only in the light-dark box. Thus, TRαAMI/Cre3 mice appear to be more likely to develop anxiety under stressful housing conditions than control mice. These results suggest that in adult mice, thyroid hormone signalling in neurons, via TRα, is involved in the control of anxiety behaviour.