Prostaglandin D2 Controls Local Blood Flow and Sleep-Promoting Neurons in the VLPO via Astrocyte-Derived Adenosine.
ACS Chem Neurosci
; 14(6): 1063-1070, 2023 03 15.
Article
in En
| MEDLINE
| ID: mdl-36847485
ABSTRACT
Prostaglandin D2 (PGD2) is one of the most potent endogenous sleep-promoting molecules. However, the cellular and molecular mechanisms of the PGD2-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 PGD2 receptors (DP1) 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 PGD2 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 PGD2 application, adenosine release induces an A2AR-mediated dilatation of blood vessels and activation of VLPO sleep-promoting neurons. Altogether, our results unravel the PGD2 signaling pathway in the VLPO, controlling local blood flow and sleep-promoting neurons, via astrocyte-derived adenosine.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prostaglandins
/
Astrocytes
Language:
En
Journal:
ACS Chem Neurosci
Year:
2023
Document type:
Article