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Updated: Mar 9, 2026
Author Spotlight: Accurately Assessing Thyroid Hormone-Driven Motor Alterations in Mouse
Published on: October 6, 2023
Neuronal expression of a thyroid hormone receptor α mutation alters mouse behaviour
S Richard1, N Aguilera2, M Thévenet3
1IGFL, INRA, Univ. Lyon 1, CNRS, ENS Lyon, 69 007 France.
Abstract:
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.
Insights
Thyroid hormone receptor alpha (TRα) in neurons influences anxiety. Disrupting TRα signaling in adult mice increased anxiety-like behaviors, especially under stress.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
- Molecular Endocrinology
Background:
- Thyroid hormone signaling is linked to mood and anxiety disorders in humans.
- Neural mechanisms connecting thyroid hormones to anxiety remain unclear.
- Thyroid hormone receptor alpha (TRα) is a key mediator of thyroid hormone action.
Purpose of the Study:
- To investigate the role of neuronal TRα in regulating anxiety-like behaviors in adult mice.
- To elucidate the neural mechanisms underlying thyroid hormone's influence on anxiety.
Main Methods:
- Utilized Cre/loxP technology to generate mice with neuron-specific dominant-negative TRα mutation (TRαAMI/Cre3).
- Assessed anxiety-like behaviors using elevated-plus maze, light-dark box, and open-field tests.
- Compared behavior under individually-housed (stressful) and group-housed conditions.
Main Results:
- TRαAMI/Cre3 mice exhibited heightened anxiety in all tests when individually housed.
- Under group housing, behavioral differences were observed only in the light-dark box test.
- Results suggest TRαAMI/Cre3 mice are more susceptible to developing anxiety under stressful conditions.
Conclusions:
- Neuronal thyroid hormone signaling, mediated by TRα, plays a significant role in controlling anxiety behavior in adult mice.
- Stressful housing conditions exacerbate anxiety-like phenotypes in mice with impaired neuronal TRα signaling.
- Findings highlight TRα as a potential therapeutic target for anxiety disorders linked to thyroid hormone dysregulation.
