12219 Hypothalamic Regucalcin Modulates Body Temperature Through Thyrotropin-releasing Hormone (trh)in Aging

Abstract Disclosure: M. Kim: None. M. Jang: None. J. Choi: None. Hypothalamic Regucalcin modulates body temperature through Thyrotropin-Releasing Hormone (TRH) in aging: Min Jun Jang[1],[2], Jeongyoon Choi[1] and Min Soo Kim[1],[3],[4]* [1] Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea, [2]Department of Convergence Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea, [3]Division of Bio-Medical Science & Technology, KIST School, Korea National University of Science and Technology (UST), Seoul 02792, Republic of Korea, [4]KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea Regucalcin (RGN), recognized as a calcium-binding protein and aging marker, plays a pivotal role in maintaining cellular homeostasis and function by contributing synthesis ascorbic acid in liver. However, the role of RGN in hypothalamus utilizing peripheral homeostasis is not unclear even the expression levels of mRNA increased in aged brain. Interestingly, the levels of RGN were decreased in other organ, including liver and kidney in aging progression. We found that RGN expression was highly increased in Medio-basal Hypothalamus (MBH) in aged mice. When we down-regulated RGN expression by using AAV-shRNA in MBH of aged mice, thermogenic activities in cold chamber were decreased compared to scramble virus injected mice (control). In addition, we found that over-expression of RGN in MHB of young mice showed increase of body temperature levels. Investigation into genes associated with TRH neuron activation, known to be stimulated under low-temperature exposure, confirmed our hypothesis, demonstrating reduced expression in TRH-related genes in mice with decreased RGN. The results suggest a vital role for hypothalamus-specific RGNs in the regulation of temperature homeostasis through the modulation of TRH neurons. Keywords: Regucalcin, RGN, Body Temperature, Thermoregulation, Cold stress, Thyroid hormone, TRH Presentation: 6/2/2024