Auflistung nach Autor:in "Maier, Julia"

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Aparecium: Revealing the role of the zona incerta in central thyroid hormone action
(2025) Maier, Julia
The importance of thyroid hormones (THs) for regulation of body temperature and energy metabolism as well as brain functions such as mood is well established. This is most evident in hypo- or hyperthyroidism, which have severe consequences on these parameters. THs exert their effects via thyroid hormone receptors α (TRα) and β (TRβ). Similar to altered ligand availability, mutations in these receptors lead to several deficits, such as defaults in neuronal development and regulation of body temperature, as well as psychomotor alterations. However, it often remains unknown whether defects are caused by TH actions directly on tissue level or centrally in the brain, and in the latter case, which brain regions mediate the central effects of THs. To address this question, PET/CT scans of mice undergoing treatment with T3 were conducted and showed activation of the Zona Incerta (ZI), a region of the subthalamus, indicating its role in mediating effects of THs. To further investigate the effect of THs in the ZI, TH signalling was inhibited by introducing a dominant-negative TRα1 via adeno-associated virus (AAV) injection into the ZI. In a separate set up, inhibition was specific to dopaminergic neurons by injecting the AAVs into tyrosine hydroxylase-Cre mice. Analysing these mice revealed that inhibited TH signalling in the ZI caused an increase in basal metabolic rate (BMR) with increased fasting weight loss without affecting body temperature. In addition, it resulted in a chronic stress-like state, in which serum corticosterone was elevated, and a partial anxiety phenotype was present, as habituation to stressful situations was impaired. However, none of these effects were observed in the conditional model, demonstrating that they were not mediated by dopaminergic neurons. Taken together, the study identifies a new brain region for central actions of THs, the ZI, and implicate it as a key brain region in TH-meditated control of behaviour and energy metabolism.