Prostaglandin D Controls Local Blood Flow and Sleep-Promoting Neurons in the VLPO via Astrocyte-Derived Adenosine.

Prostaglandin D (PGD) is one of the most potent endogenous sleep-promoting molecules. However, the cellular and molecular mechanisms of the PGD-induced activation of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO), the major nonrapid eye movement (NREM)-sleep center, still remains unclear. We here show that PGD receptors (DP) are not only expressed in the leptomeninges but also in astrocytes from the VLPO. We further demonstrate, by performing real-time measurements of extracellular adenosine using purine enzymatic biosensors in the VLPO, that PGD application causes a 40% increase in adenosine level, via an astroglial release. Measurements of vasodilatory responses and electrophysiological recordings finally reveal that, in response to PGD application, adenosine release induces an AR-mediated dilatation of blood vessels and activation of VLPO sleep-promoting neurons. Altogether, our results unravel the PGD signaling pathway in the VLPO, controlling local blood flow and sleep-promoting neurons, via astrocyte-derived adenosine.