Most mammalian cells have molecular circadian clocks that generate widespread rhythms in transcript and protein abundance. While circadian clocks are robust to fluctuations in the cellular environment, little is known about the mechanisms by which the circadian period compensates for fluctuating metabolic states. Here, we exploit the heterogeneity of single cells both in circadian period and a metabolic parameter-protein stability-to study their interdependence without the need for genetic manipulation. We generated cells expressing key circadian proteins (CRYPTOCHROME1/2 (CRY1/2) and PERIOD1/2 (PER1/2)) as endogenous fusions with fluorescent proteins and simultaneously monitored circadian rhythms and degradation in thousands of single cells. We found that the circadian period compensates for fluctuations in the turnover rates of circadian repressor proteins and uncovered possible mechanisms using a mathematical model. In addition, the stabilities of the repressor proteins are circadian phase dependent and correlate with the circadian period in a phase-dependent manner, in contrast to the prevailing model.
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http://dx.doi.org/10.1073/pnas.2404738121 | DOI Listing |
Biochem J
December 2024
Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati College of Medicine, Cincinnati, OH, U.S.A.
In mammals, molecular mechanisms of circadian rhythms involve a time-delayed negative feedback loop generating autonomous oscillations of ∼24 h. Most cell types in mammals possess circadian rhythms regulating temporal organization of cellular and physiological processes. Intriguingly, pluripotent stem cells do not possess circadian rhythms and oscillations arise after a defined period of differentiation.
View Article and Find Full Text PDFJ Pineal Res
November 2024
School of Neurobiology, Biochemistry and Biophysics, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel Aviv, Israel.
Located dorsally underneath a thin translucent skull in many teleosts, the pineal gland is a photoreceptive organ known as a key element of the circadian clock system. Nevertheless, the presence of additional routes of photoreception presents a challenge in determining its specific roles in regulating photic-related behavior. Here, we show the importance of the pineal gland in mediating a prolonged motor response of zebrafish larvae to sudden darkness, both as a photodetector and as a circadian pacemaker.
View Article and Find Full Text PDFKorean J Pain
December 2024
School of Anesthesia, Shanxi Medical University, Shanxi, China.
Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats.
View Article and Find Full Text PDFZebrafish
December 2024
Department of Life Sciences and Biotechnology, Faculty of Biology, University of Ferrara, Ferrara, Italy.
Photoperiod and temperature are two of the most powerful environmental cues that entrain circadian clocks. Being ectothermic, fish must keep their body temperature within a physiological range to optimize biological processes mainly applying behavioral strategies. Here, we developed a low-cost, automated system that allows to create a horizontal multiple-step thermal gradient and video record fish behavior for long-term periods.
View Article and Find Full Text PDFBrain Behav
December 2024
Neuroscience Institute, Georgia State University, Atlanta, Georgia, USA.
Purpose: Perineuronal nets (PNNs) are extracellular matrix proteoglycans surrounding neurons and glia. It has been suggested that PNNs are involved in the pathophysiology of multiple CNS illnesses, including stress-related neuropsychiatric disorders like schizophrenia, major depressive disorder, and anxiety disorders.
Method: Before examining the putative role of PNNs in stress-related responses, we described for the first time the anatomical distribution in Syrian hamsters (Mesocricetus auratus), an excellent model organism for studying social stress and circadian rhythms.
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