Publications by authors named "Karolína Liška"

5 Publications

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Hormonal fine-tuning of clock in decidual region of mouse placenta by dopamine, melatonin, insulin, leptin and ghrelin.

Placenta 2021 May 27;108:55-63. Epub 2021 Mar 27.

Laboratory of Biological Rhythms, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic. Electronic address:

Introduction: The maternal part of the rodent placenta harbors a circadian clock which robustly responds to glucocorticoids, however, its sensitivity to other hormones has not been elucidated. In this study, we tested five selected hormones (dopamine, melatonin, insulin, leptin and ghrelin) for their effectiveness to affect the clock in decidual region of mouse placenta in vitro.

Methods: We administered the hormones or corresponding vehicles at various time points over 24 h to organotypic placental explants of mPer2 mice containing the decidua basalis (DB) region and monitored their effects on amplitude, period, median expression level (mesor) and phase of PER2-driven bioluminescence rhythms.

Results: Dopamine significantly increased the amplitude, robustly dampened the mesor, and during a narrow time interval (corresponding to daytime) induced phase delays of the rhythms. In contrast, melatonin had no effect on amplitude, but induced phase advances of the rhythms at the opposite time window than dopamine (corresponding to nighttime). Leptin and ghrelin, but not insulin, slightly increased amplitudes and moderately modulated phase delays of the clock, suggesting that the DB clock, in contrast to other peripheral clocks, is rather resilient to abrupt changes in levels of feeding- and metabolism-related hormones.

Discussion: The results demonstrate for the first time that dopamine and melatonin exhibit delicate yet specific effects on parameters of the DB clock and may thus potentially contribute to fine-tuning of its phase under in vivo conditions. It also implies that dysregulation of their levels, which accompany various pathologies, may account for malfunction of the clock in DB.
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http://dx.doi.org/10.1016/j.placenta.2021.03.015DOI Listing
May 2021

Challenging the Integrity of Rhythmic Maternal Signals Revealed Gene-Specific Responses in the Fetal Suprachiasmatic Nuclei.

Front Neurosci 2020 7;14:613531. Epub 2021 Jan 7.

Laboratory of Biological Rhythms, Institute of Physiology, Czech Academy of Sciences, Prague, Czechia.

During fetal stage, maternal circadian system sets the phase of the developing clock in the suprachiasmatic nuclei (SCN) via complex pathways. We addressed the issue of how impaired maternal signaling due to a disturbed environmental light/dark (LD) cycle affects the fetal SCN. We exposed pregnant Wistar rats to two different challenges - a 6-h phase shift in the LD cycle on gestational day 14, or exposure to constant light (LL) throughout pregnancy - and detected the impact on gene expression profiles in 19-day-old fetuses. The LD phase shift, which changed the maternal SCN into a transient state, caused robust downregulation of expression profiles of clock genes (, , and ), clock-controlled () genes, as well as genes involved in sensing various signals, such as and . Removal of the rhythmic maternal signals via exposure of pregnant rats to LL abolished the rhythms in expression of and in the fetal SCN. We identified as the gene primarily responsible for sensing rhythmic maternal signals because its expression profile tracked the shifted or arrhythmic maternal SCN clock. Pathways related to the maternal rhythmic behavioral state were likely not involved in driving the expression rhythm. Instead, introduction of a behavioral rhythm to LL-exposed mothers via restricted feeding regime strengthened rhythm in expression in the fetal SCN. Our results revealed for the first time that the fetal SCN is highly sensitive in a gene-specific manner to various changes in maternal signaling due to disturbances of environmental cycles related to the modern lifestyle in humans.
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http://dx.doi.org/10.3389/fnins.2020.613531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817817PMC
January 2021

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 2021 03 12;185:108455. Epub 2021 Jan 12.

The Czech Academy of Sciences, Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4, 14220, Czech Republic.

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.
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http://dx.doi.org/10.1016/j.neuropharm.2021.108455DOI Listing
March 2021

Glucocorticoids reset circadian clock in choroid plexus via period genes.

J Endocrinol 2021 Feb;248(2):155-166

Laboratory of Biological Rhythms, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.

The epithelial cells of choroid plexus (CP) in brain ventricles produce cerebrospinal fluid and act as the blood-cerebrospinal fluid barrier. In this study, we confirmed that CP in the 4th ventricle is composed of cellular oscillators that all harbor glucocorticoid receptors and are mutually synchronized to produce a robust clock gene expression rhythm detectable at the tissue level in vivo and in vitro. Animals lacking glucocorticoids (GCs) due to surgical removal of adrenal glands had Per1, Per2, Nr1d1 and Bmal1 clock gene rhythmicity in their CP significantly dampened, whereas subjecting them to daily bouts of synthetic GC analog, dexamethasone (DEX), reinforced those rhythms. We verified these in vivo effects using an in vitro model of organotypic CP explants; depending on the time of its application, DEX significantly increased the amplitude and efficiently reset the phase of the CP clock. The results are the first description of a PRC for a non-neuronal clock in the brain, demonstrating that CP clock shares some properties with the non-neuronal clocks elsewhere in the body. Finally, we found that DEX exhibited multiple synergic effects on the CP clock, including acute activation of Per1 expression and change of PER2 protein turnover rate. The DEX-induced shifts of the CP clock were partially mediated via PKA-ERK1/2 pathway. The results provide the first evidence that the GC rhythm strengthens and entrains the clock in the CP helping thus fine-tune the brain environment according to time of day.
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http://dx.doi.org/10.1530/JOE-20-0526DOI Listing
February 2021