Number of the records: 1
Modulation of single cell circadian response to NMDA by diacylglycerol lipase inhibition reveals a role of endocannabinoids in light entrainment of the suprachiasmatic nucleus
- 1.
SYSNO ASEP 0541524 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Modulation of single cell circadian response to NMDA by diacylglycerol lipase inhibition reveals a role of endocannabinoids in light entrainment of the suprachiasmatic nucleus Author(s) Sládek, Martin (FGU-C) RID, ORCID, SAI
Liška, Karolína (FGU-C) ORCID
Houdek, Pavel (FGU-C) ORCID
Sumová, Alena (FGU-C) RID, ORCIDArticle number 108455 Source Title Neuropharmacology. - : Elsevier - ISSN 0028-3908
Roč. 185, Mar 1 (2021)Number of pages 12 s. Language eng - English Country NL - Netherlands Keywords circadian ; suprachiasmatic nucleus ; N-Methyl-D-aspartate ; endocannabinoids ; PER2::LUC ; phase response curve Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects GA17-14704S GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support FGU-C - RVO:67985823 UT WOS 000620271500003 EID SCOPUS 85099350268 DOI 10.1016/j.neuropharm.2021.108455 Annotation Suprachiasmatic nucleus (SCN) of the hypothalamus is the master clock that drives circadian rhythms in physiology and behavior and adjusts their timing to external cues. Neurotransmitter glutamate and glutamatergic receptors sensitive to N-methyl-D-aspartate (NMDA) play a dual role in the SCN by coupling astrocytic and neuronal single cell oscillators and by resetting their phase in response to light. Recent reports suggested that signaling by endogenous cannabinoids (ECs) participates in both of these functions. We have previously shown that ECs, such as 2-arachidonoylglycerol (2-AG), act via CB1 receptors to affect the SCN response to light-mimicking NMDA stimulus in a time-dependent manner. We hypothesized that this ability is linked to the circadian regulation of EC signaling. We demonstrate that circadian clock in the rat SCN regulates expression of 2-AG transport, synthesis and degradation enzymes as well as its receptors. Inhibition of the major 2-AG synthesis enzyme, diacylglycerol lipase, enhanced the phase delay and lowered the amplitude of explanted SCN rhythm in response to NMDAR activation. Using microscopic PER2 bioluminescence imaging, we visualized how individual single cell oscillators in different parts of the SCN respond to the DAGL inhibition/NMDAR activation and shape response of the whole pacemaker. Additionally, we present strong evidence that the zero amplitude behavior of the SCN in response to single NMDA stimulus in the middle of subjective night is the result of a loss of rhythm in individual SCN cells. The paper provides new insights into the modulatory role of endocannabinoid signaling during the light entrainment of the SCN. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://doi.org/10.1016/j.neuropharm.2021.108455
Number of the records: 1