A Neural Circuit Underlying the Generation of Hot Flushes

Abstract

Summary: Hot flushes are a sudden feeling of warmth commonly associated with the decline of gonadal hormones at menopause. Neurons in the arcuate nucleus of the hypothalamus that express kisspeptin and neurokinin B (Kiss1ARH neurons) are candidates for mediating hot flushes because they are negatively regulated by sex hormones. We used a combination of genetic and viral technologies in mice to demonstrate that artificial activation of Kiss1ARH neurons evokes a heat-dissipation response resulting in vasodilation (flushing) and a corresponding reduction of core-body temperature in both females and males. This response is sensitized by ovariectomy. Brief activation of Kiss1ARH axon terminals in the preoptic area of the hypothalamus recapitulates this response, while pharmacological blockade of neurokinin B (NkB) receptors in the same brain region abolishes it. We conclude that transient activation of Kiss1ARH neurons following sex-hormone withdrawal contributes to the occurrence of hot flushes via NkB release in the rostral preoptic area. : The underlying cause of hot flushes is poorly understood. Padilla et al. provide evidence that a subpopulation of hypothalamic neurons can generate hot flush symptoms in mice. Establishing the mechanism of hot flush generation may allow for the development of therapies. Keywords: hot flashes, temperature regulation, neurokinin B, kisspeptin, menopause, estrogen, optogenetics, chemogenetics