Scharbarg Emeric, Walter Augustin, Lecoin Laure, Gallopin Thierry, Lemaître Frédéric, Guille-Collignon Manon, Rouach Nathalie, Rancillac Armelle
Brain Plasticity Unit, CNRS, ESPCI-ParisTech, Labex Memolife, Université PSL, 75005 Paris, France.
Neuroglial Interactions in Cerebral Physiology and Pathologies, Center for Interdisciplinary Research in Biology, Collège de France, CNRS, Inserm, Labex Memolife, Université PSL, 75005 Paris, France.
ACS Chem Neurosci. 2023 Mar 15;14(6):1063-1070. doi: 10.1021/acschemneuro.2c00660. Epub 2023 Feb 27.
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.
前列腺素D（PGD）是最有效的内源性促睡眠分子之一。然而，PGD诱导腹外侧视前核（VLPO，主要的非快速眼动睡眠中心）中促睡眠神经元激活的细胞和分子机制仍不清楚。我们在此表明，PGD受体（DP）不仅在软脑膜中表达，也在VLPO的星形胶质细胞中表达。我们通过在VLPO中使用嘌呤酶生物传感器对细胞外腺苷进行实时测量进一步证明，应用PGD会通过星形胶质细胞释放使腺苷水平增加40%。血管舒张反应测量和电生理记录最终揭示，响应PGD应用，腺苷释放诱导由AR介导的血管舒张和VLPO促睡眠神经元的激活。总之，我们的结果揭示了VLPO中通过星形胶质细胞衍生的腺苷控制局部血流和促睡眠神经元的PGD信号通路。
