Sidney Pereira, PhD
Sidney A. Pereira, Liliana Arvizu-Sanchez, Rona S. Carroll, Victor M. Navarro, Ursula B. Kaiser
Ursula B. Kaiser and Victor M. Navarro
Research Category: Neurosciences
The interaction between glucocorticoids and menopause-related conditions such as thermoregulatory changes remains unclear. KNDy neurons, expressing Kisspeptin, Neurokinin-B and Dynorphin-A, project to thermoregulatory neurons and are proposed to trigger vasomotor symptoms during menopause or hypogonadism. KNDy neurons are regulated by multiple neural networks, among which GABAergic neurons play a determinant role. To investigate whether the actions of glucocorticoids on thermoregulation occur through glucocorticoid receptor (GR)-expressing GABAergic neurons, we generated mice with conditional deletion of GR in GABAergic neurons, crossing VgatCre with GRlox/lox mice to generate GABAGRKO mice. Intact GABAGRKO and control males had similar core (Tc) and skin (Tsk) temperatures. Similarly, 7 days after ovariectomy and estradiol replacement, GABAGRKO and control females had similar Tc and Tsk. However, 14 days after estradiol removal, Tc and Tsk increased more in GABAGRKO females than in controls. Conversely, gonadectomy (GDX) in males for 14 days increased both Tc and Tsk in controls, while GABAGRKO males remained unchanged for Tc but had increased Tsk. Lack of GR in GABAergic neurons results in sexually dimorphic changes in Tc and Tsk in GDX-GABAGRKO mice. Our findings suggest a role of glucocorticoids acting on GR-expressing GABAergic neurons upstream of KNDy neurons to modulate the thermoregulatory system.
Reproductive aging in women is invariably accompanied by the lack of sex hormones at the time of menopause. This loss has been linked to adverse health outcomes including hot flashes, sleep disruption, impaired quality of life, obesity, and heart diseases susceptibility. The interaction between stress and hot flashes is debated and remains relatively unclear. The overall goal of this study was to determine the mechanisms/pathways underlying the effects of stress on hot flashes. Using female and male castrated mice (model that mimics menopause in mouse), our preliminary results have shown that specific neurons in the brain (GABAergic neurons) are responsible to mediate the effects of stress on hot flashes in a sex-dependent manner.