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Estrogen Sensitive Neurons in the Medial Preoptic Area of the Hypothalamus Regulate Temperature in Mice


Reduced estrogen levels in menopausal and perimenopausal women are associated with hot flashes. The medial preoptic area (MPA) of the hypothalamus is region of the brain with many physiological functions including temperature regulation. While this region of the brain is rich in estrogen responsive neurons, it is unknown whether or not estrogen plays a role in the MPA’s temperature regulation. Thus, we hypothesized that temperature sensitive neurons in the MPA are responsive to estrogen and could mediate thermoregulation via thermogenesis and heat dissipation. To define the role of estrogen sensitive neurons in the MPA we selectively activated the neurons using chemogenetics or ablated by delivering a virus expressing caspase3 into Esr1-Cre mice. We recorded core body temperature using intraperitoneal telemetry probes. Ablation of the neurons led to an increase in core body temperature. In contrast, chemogenetic activation of the neurons led to a drop in core body temperature. Thermogenesis of brown adipose tissue (BAT) and head dissipation of skin temperature on the tail were observed using an infrared camera and analysis software. Upon activation, there was a decrease in temperature of BAT suggesting a reduction of thermogenesis. We also observed an initial increase in tail temperature suggesting vasodilation and a release of heat, lowering core body temperature. To further analyze the MPA’s role in temperature regulation we took advantage of the physiological state of torpor which mice enter upon fasting. Torpor is associated with a decrease in temperature, metabolism, activity, cardiac function, and mental activity. We saw that ablation of estrogen sensitive neurons in the MPA impedes the temperature drop seen in torpor. These complementary loss of function and gain of function studies suggest a critical role for estrogen signaling in the MPA in temperature regulation. Building an understanding of the estrogen-sensitive temperature populations of the brain will help model and study hot flashes.

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