Endocrine Abstracts

Thyroid hormones (TH) play a regulatory role in growth and development as well as cardiovascular function and thermogenesis. Furthermore, an excess of TH can cause anxiety and nervousness in hyperthyroid patients. While the direct effects of an imbalance in the TH system on peripheral organs like the heart and the liver are well studied, there is evidence of a central component of regulation. In this project, we aim to understand the contributions of the central nervous system in the T3-dependent regulation of the cardiovascular system and anxiety-like behavior. Using a Cre transgenic mouse line in combination with a stereotaxic injection of an AAV carrying the gene for a dominant negative TRα1, we generated mice with impaired TRα1 signaling in the parvalbumin-expressing population of hypothalamic and hippocampal GABAergic neurons, respectively. Given the impact of parvalbumin neurons in the hypothalamus on cardiovascular parameters such as blood pressure and heart rate frequency distribution, the model allowed us to investigate the contribution of central TRα1 signaling to the regulation of cardiovascular function. Continuous radiotelemetry recordings of heart rate and body temperature as well as ECG measurements were utilized in this study. Using the animal model with an impaired hippocampal TRα1 signaling in parvalbumin neurons, we investigated the TH-dependent effects of this hippocampal cell population on anxiety-like behavior as well as memory function and metabolism. Our findings demonstrate that this AAV-based method can be utilized to elucidate the consequences of a cell-specific hypothyroidism in targeted neurons, shedding light on the role of local thyroid hormone action in parvalbumin neurons in the regulation of behavior and cardiovascular functions.