Počet záznamů: 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. 1.
    0541524 - FGÚ 2022 RIV NL eng J - Článek v odborném periodiku
    Sládek, Martin - Liška, Karolína - Houdek, Pavel - Sumová, Alena
    Modulation of single cell circadian response to NMDA by diacylglycerol lipase inhibition reveals a role of endocannabinoids in light entrainment of the suprachiasmatic nucleus.
    Neuropharmacology. Roč. 185, Mar 1 (2021), č. článku 108455. ISSN 0028-3908. E-ISSN 1873-7064
    Grant CEP: GA ČR(CZ) GA17-14704S
    Institucionální podpora: RVO:67985823
    Klíčová slova: circadian * suprachiasmatic nucleus * N-Methyl-D-aspartate * endocannabinoids * PER2::LUC * phase response curve
    Obor OECD: Physiology (including cytology)
    Impakt faktor: 5.250, rok: 2020
    Způsob publikování: Omezený přístup
    https://doi.org/10.1016/j.neuropharm.2021.108455

    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.
    Trvalý link: http://hdl.handle.net/11104/0319091

     
     
Počet záznamů: 1