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Prostaglandin D2 Controls Local Blood Flow and Sleep-Promoting Neurons in the VLPO via Astrocyte-Derived Adenosine
Emeric Scharbarg1, Augustin Walter2, Laure Lecoin2
1Brain Plasticity Unit, CNRS, ESPCI-ParisTech, Labex Memolife, Université PSL, 75005 Paris, France.
ACS Chemical Neuroscience
|February 27, 2023
Summary
Prostaglandin D2 (PGD2) promotes sleep by activating neurons in the ventrolateral preoptic nucleus (VLPO). This study reveals PGD2 triggers astrocyte-released adenosine, which enhances sleep-promoting neuron activity and blood flow.
Area of Science:
- Neuroscience
- Sleep Research
- Molecular Biology
Background:
- Prostaglandin D2 (PGD2) is a key molecule for promoting sleep.
- The precise mechanisms of PGD2-induced sleep promotion in the ventrolateral preoptic nucleus (VLPO) remain largely unknown.
- The VLPO is a critical center for nonrapid eye movement (NREM) sleep regulation.
Purpose of the Study:
- To elucidate the cellular and molecular pathways through which PGD2 activates sleep-promoting neurons in the VLPO.
- To investigate the role of astrocytes and adenosine in PGD2-mediated sleep regulation.
Main Methods:
- Investigated Prostaglandin D2 receptor 1 (DP1) expression in VLPO astrocytes.
- Measured extracellular adenosine levels in the VLPO using purine enzymatic biosensors.
- Assessed vasodilatory responses and performed electrophysiological recordings in the VLPO.
Main Results:
- DP1 receptors are expressed in VLPO astrocytes.
- PGD2 application significantly increased extracellular adenosine levels in the VLPO, mediated by astrocytes.
- Adenosine release induced by PGD2 resulted in A2A receptor-mediated vasodilation and activation of sleep-promoting neurons.
Conclusions:
- PGD2 signaling in the VLPO involves astrocyte-derived adenosine.
- This pathway controls local blood flow and activates sleep-promoting neurons, contributing to NREM sleep.
- The findings reveal a novel PGD2-astrocyte-adenosine pathway crucial for sleep regulation.
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