Prostaglandin D 2 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 rem...

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Published in:ACS chemical neuroscience 2023-03, Vol.14 (6), p.1063-1070
Main Authors: Scharbarg, Emeric, Walter, Augustin, Lecoin, Laure, Gallopin, Thierry, Lemaître, Frédéric, Guille-Collignon, Manon, Rouach, Nathalie, Rancillac, Armelle
Format: Article
Language:English
Subjects:
Adenosine - metabolism
Astrocytes - metabolism
Life Sciences
Neurobiology
Neurons - metabolism
Neurons and Cognition
Prostaglandin D2 - pharmacology
Prostaglandin D2 - physiology
Prostaglandins
Sleep
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Summary: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 A R-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.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.2c00660