title: Neuronal expression of a thyroid hormone receptor α mutation alters mouse behaviour.
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.
authors.affiliation: IGFL, INRA, Univ. Lyon 1, CNRS, ENS Lyon, 69 007 France. Electronic address: sabine.richard@ens-lyon.fr.
authors.forename: S
authors.initials: S
authors.lastname: Richard
authors.affiliation: PBES, SFR Biosciences, INSERM, CNRS UMS3444, Univ. Lyon 1, ENS Lyon, France.
authors.forename: N
authors.initials: N
authors.lastname: Aguilera
authors.affiliation: CRNL, CNRS, Lyon, France. Electronic address: mthevenet@olfac.univ-lyon1.fr.
authors.forename: M
authors.initials: M
authors.lastname: Thévenet
authors.affiliation: INSERM U846, Stem-cell and Brain Research Institute, Department of Chronobiology, University of Lyon 1, 69003 Lyon, France. Electronic address: ouria.benyahya@inserm.fr.
authors.forename: O
authors.initials: O
authors.lastname: Dkhissi-Benyahya
authors.affiliation: IGFL, INRA, Univ. Lyon 1, CNRS, ENS Lyon, 69 007 France. Electronic address: frederic.flamant@ens-lyon.fr.
authors.forename: F
authors.initials: F
authors.lastname: Flamant
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000473:pathology; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002940:Circadian Rhythm / Q000502:physiology; D003863:Depression / Q000378:metabolism / Q000473:pathology; D005260:Female; D006799:Housing, Animal; D007037:Hypothyroidism / Q000378:metabolism / Q000523:psychology; D008297:Male; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009154:Mutation; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics / Q000378:metabolism*; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones
keywords: Animal model; Anxiety; Brain; Conditional gene targeting; Hypothyroidism