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Inhibition of Thyroid Hormone Signaling in the Zona Incerta Alters Basal Metabolic Rate, Behavior, and Serum Glucocorticoids in Male Mice.

Authors :
Maier, Julia
Dore, Riccardo
Oelkrug, Rebecca
Glatzel, Annika
Cremer, Anna-Lena
Binder, Sonja
Schwaninger, Markus
Oster, Henrik
Backes, Heiko
Mittag, Jens
Source :
Thyroid. Oct2024, Vol. 34 Issue 10, p1280-1291. 12p.
Publication Year :
2024

Abstract

Background: It has long been known that thyroid disease can lead to changes in energy metabolism, thermoregulation, and anxiety behavior. While these actions have been partially attributed to thyroid hormone (TH) receptor α1 (TRα1) action in the brain, the precise neuroanatomical substrates have remain elusive. Methods: We used PET-CT scans to identify brain regions affected by TH. We then inhibited TRα1 signaling specifically in the most affected region, the zona incerta (ZI), a still mysterious region previously implicated in thermogenesis and anxiety. To this end, we used an adeno-associated virus (AAV) expressing a dominant-negative TRα1R384C in wild-type mice and phenotyped the animals. Finally, we used tyrosine hydroxylase-Cre mice to test specifically the contribution of ZI dopaminergic neurons. Results: Our data showed that AAV-mediated inhibition of TRα1 signaling in the ZI lead to increased energy expenditure at thermoneutrality, while body temperature regulation remained unaffected. Moreover, circulating glucocorticoid levels were increased, and a mild habituation problem was observed in the open field test. No effects were observed when TRα1 signaling was selectively inhibited in dopaminergic neurons. Conclusions: Our findings suggest that altered TH signaling in the ZI is not involved in body temperature regulation but can affect basal metabolism and modulates stress responses. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
10507256
Volume :
34
Issue :
10
Database :
Academic Search Index
Journal :
Thyroid
Publication Type :
Academic Journal
Accession number :
180233658
Full Text :
https://doi.org/10.1089/thy.2024.0209