Circadian Entrainment to Temperature, But Not Light, in the Isolated Suprachiasmatic Nucleus

2003 ◽  
Vol 90 (2) ◽  
pp. 763-770 ◽  
Author(s):  
Erik D. Herzog ◽  
Rachel M. Huckfeldt
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Temperature Compensation ◽  
Brain Temperature ◽  
Fundamental Properties ◽  
Daily Cycles ◽  
Individual Mouse ◽  
And Behavior ◽  
Circadian Pacemakers

The suprachiasmatic nucleus (SCN) is the master pacemaker that drives circadian rhythms in mammalian physiology and behavior. The abilities to synchronize to daily cycles in the environment and to keep accurate time over a range of physiologic temperatures are two fundamental properties of circadian pacemakers. Recordings from a bioluminescent reporter ( Per1-luc) of Period1 gene activity in rats showed that the cultured SCN entrained to daily, 1.5°C cycles of temperature, but did not synchronize to daily light cycles. Temperature entrainment developed by 1 day after birth. Light cycles failed to affect the isolated SCN of rats aged 2 to 339 days. Entrainment to a 3-h shift in the warm-cool cycle was possible in <3 days with 3°C cycles. Importantly, Per1-luc expression in vitro was similar to that seen in vivo where peak expression occurs approximately 1 h prior to the daily increase in temperature. In addition, the firing rate of individual mouse SCN neurons continued to express near 24-h rhythms from 24–37°C. At lower temperatures, the percentage of rhythmic cells was reduced, but periodicity was temperature compensated. The results indicate that normal rhythms in brain temperature may serve to stabilize rhythmicity of the circadian system in vivo and that temperature compensation of this period is determined at the level of individual SCN cells.

scholarly journals Circadian clock neurons mediate time-of-day dependent responses to light

2018 ◽  
Author(s):  
Jeff R. Jones ◽  
Tatiana Simon ◽  
Lorenzo Lones ◽  
Erik D. Herzog
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Time Of Day ◽  
Light Cycle ◽  
Hormone Release ◽  
Daily Rhythms ◽  
Light Responses ◽  
And Behavior

ABSTRACTCircadian (~24 h) rhythms influence nearly all aspects of physiology, including sleep/wake, metabolism, and hormone release. The suprachiasmatic nucleus (SCN) synchronizes these daily rhythms to the external light cycle, but the mechanisms by which this occurs is unclear. The neuropeptide vasoactive intestinal peptide (VIP) is the predominant contributor to synchrony within the SCN and is important for circadian light responses, but the role of VIP neurons themselves is unclear. Thus, we tested the hypothesis that rhythmic SCN VIP neurons mediate circadian light responses. Using in vivo fiber photometry recording of SCN VIP neurons we found daily rhythms in spontaneous calcium events that peaked during the subjective day and in light-evoked calcium events that exhibited the greatest response around subjective dusk. These rhythms were correlated with spontaneous and NMDA-evoked VIP release from SCN VIP neurons in vitro. Finally, in vivo hyperpolarization of VIP neurons attenuated light-induced shifts of daily rhythms in locomotion. We conclude that SCN VIP neurons are circadian and depolarize to light to modulate entrainment of daily rhythms in the SCN and behavior.

scholarly journals Redox Polymers for Tissue Engineering

2021 ◽  
Vol 3 ◽  
Author(s):  
Binbin Z. Molino ◽  
Junji Fukuda ◽  
Paul J. Molino ◽  
Gordon G. Wallace
Keyword(s):  
Tissue Engineering ◽  
Conducting Polymers ◽  
Polymeric Materials ◽  
Redox Polymers ◽  
Design Synthesis ◽  
Materials Development ◽  
Biologically Relevant ◽  
Fundamental Properties

This review will focus on the targeted design, synthesis and application of redox polymers for use in regenerative medicine and tissue engineering. We define redox polymers to encompass a variety of polymeric materials, from the multifunctional conjugated conducting polymers to graphene and its derivatives, and have been adopted for use in the engineering of several types of stimulus responsive tissues. We will review the fundamental properties of organic conducting polymers (OCPs) and graphene, and how their properties are being tailored to enhance material - biological interfacing. We will highlight the recent development of high-resolution 3D fabrication processes suitable for biomaterials, and how the fabrication of intricate scaffolds at biologically relevant scales is providing exciting opportunities for the application of redox polymers for both in-vitro and in-vivo tissue engineering. We will discuss the application of OCPs in the controlled delivery of bioactive compounds, and the electrical and mechanical stimulation of cells to drive behaviour and processes towards the generation of specific functional tissue. We will highlight the relatively recent advances in the use of graphene and the exploitation of its physicochemical and electrical properties in tissue engineering. Finally, we will look forward at the future of organic conductors in tissue engineering applications, and where the combination of materials development and fabrication processes will next unite to provide future breakthroughs.

scholarly journals Glucocorticoid receptor action in metabolic and neuronal function

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Health And Disease ◽  
And Behavior ◽  
External Signals ◽  
The Brain

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

scholarly journals Morphine-induced synaptic plasticity in the VTA is reversed by HDAC inhibition

2016 ◽  
Vol 116 (3) ◽  
pp. 1093-1103 ◽  
Author(s):  
Michael E. Authement ◽  
Ludovic D. Langlois ◽  
Haifa Kassis ◽  
Shawn Gouty ◽  
Matthieu Dacher ◽  
...  
Keyword(s):  
Behavioral Plasticity ◽  
Drugs Of Abuse ◽  
Patch Clamp Recording ◽  
Whole Cell Patch Clamp ◽  
Synaptic Changes ◽  
Induced Changes ◽  
And Behavior ◽  
H3 Acetylation

Dopamine (DA) dysfunction originating from the ventral tegmental area (VTA) occurs as a result of synaptic abnormalities following consumption of drugs of abuse and underlies behavioral plasticity associated with drug abuse. Drugs of abuse can cause changes in gene expression through epigenetic mechanisms in the brain that underlie some of the lasting neuroplasticity and behavior associated with addiction. Here we investigated the function of histone acetylation and histone deacetylase (HDAC)2 in the VTA in recovery of morphine-induced synaptic modifications following a single in vivo exposure to morphine. Using a combination of immunohistochemistry, Western blot, and whole cell patch-clamp recording in rat midbrain slices, we show that morphine increased HDAC2 activity in VTA DA neurons and reduced histone H3 acetylation at lysine 9 (Ac-H3K9) in the VTA 24 h after the injection. Morphine-induced synaptic changes at glutamatergic synapses involved endocannabinoid signaling to reduce GABAergic synaptic strength onto VTA DA neurons. Both plasticities were recovered by in vitro incubation of midbrain slices with a class I-specific HDAC inhibitor (HDACi), CI-994, through an increase in acetylation of histone H3K9. Interestingly, HDACi incubation also increased levels of Ac-H3K9 and triggered GABAergic and glutamatergic plasticities in DA neurons of saline-treated rats. Our results suggest that acute morphine-induced changes in VTA DA activity and synaptic transmission engage HDAC2 activity locally in the VTA to maintain synaptic modifications through histone hypoacetylation.

scholarly journals Temporally chimeric mice reveal flexibility of circadian period-setting in the suprachiasmatic nucleus

2016 ◽  
Vol 113 (13) ◽  
pp. 3657-3662 ◽  
Author(s):  
Nicola J. Smyllie ◽  
Johanna E. Chesham ◽  
Ryan Hamnett ◽  
Elizabeth S. Maywood ◽  
Michael H. Hastings
Keyword(s):  
Gene Expression ◽  
Suprachiasmatic Nucleus ◽  
Feedback Loops ◽  
Chimeric Mice ◽  
Pacemaker Cells ◽  
Daily Behavior ◽  
New Perspective ◽  
Circadian Behavior

The suprachiasmatic nucleus (SCN) is the master circadian clock controlling daily behavior in mammals. It consists of a heterogeneous network of neurons, in which cell-autonomous molecular feedback loops determine the period and amplitude of circadian oscillations of individual cells. In contrast, circuit-level properties of coherence, synchrony, and ensemble period are determined by intercellular signals and are embodied in a circadian wave of gene expression that progresses daily across the SCN. How cell-autonomous and circuit-level mechanisms interact in timekeeping is poorly understood. To explore this interaction, we used intersectional genetics to create temporally chimeric mice with SCN containing dopamine 1a receptor (Drd1a) cells with an intrinsic period of 24 h alongside non-Drd1a cells with 20-h clocks. Recording of circadian behavior in vivo alongside cellular molecular pacemaking in SCN slices in vitro demonstrated that such chimeric circuits form robust and resilient circadian clocks. It also showed that the computation of ensemble period is nonlinear. Moreover, the chimeric circuit sustained a wave of gene expression comparable to that of nonchimeric SCN, demonstrating that this circuit-level property is independent of differences in cell-intrinsic periods. The relative dominance of 24-h Drd1a and 20-h non-Drd1a neurons in setting ensemble period could be switched by exposure to resonant or nonresonant 24-h or 20-h lighting cycles. The chimeric circuit therefore reveals unanticipated principles of circuit-level operation underlying the emergent plasticity, resilience, and robustness of the SCN clock. The spontaneous and light-driven flexibility of period observed in chimeric mice provides a new perspective on the concept of SCN pacemaker cells.

scholarly journals Folate-Targeted Monodisperse PEG-Based Conjugates Made by Chemo-Enzymatic Methods for Cancer Diagnosis and Treatment

2021 ◽  
Vol 22 (19) ◽  
pp. 10347
Author(s):  
Krisztina S. Nagy ◽  
Krisztina Toth ◽  
Eva Pallinger ◽  
Angela Takacs ◽  
Laszlo Kohidai ◽  
...  
Keyword(s):  
Unique Feature ◽  
Intratumoral Injection ◽  
Metal Catalyst ◽  
Flow Cytometry Analysis ◽  
Delay Tumor Growth ◽  
In Vivo Testing ◽  
And Behavior ◽  
Full Conversion

This paper focuses on preliminary in vitro and in vivo testing of new bivalent folate-targeted PEGylated doxorubicin (DOX) made by modular chemo-enzymatic processes (FA2-dPEG-DOX2). A unique feature is the use of monodisperse PEG (dPEG). The modular approach with enzyme catalysis ensures exclusive γ-conjugation of folic acid, full conversion and selectivity, and no metal catalyst residues. Flow cytometry analysis showed that at 10 µM concentration, both free DOX and FA2-dPEG-DOX2 would be taken up by 99.9% of triple-negative breast cancer cells in 2 h. Intratumoral injection to mice seemed to delay tumor growth more than intravenous delivery. The mouse health status, food, water consumption, and behavior remained unchanged during the observation.

Fly-on-a-Chip: Microfluidics for Drosophila melanogaster Studies

2019 ◽  
Vol 11 (12) ◽  
pp. 425-443 ◽  
Author(s):  
Alireza Zabihihesari ◽  
Arthur J Hilliker ◽  
Pouya Rezai
Keyword(s):  
Drosophila Melanogaster ◽  
Developmental Stages ◽  
Model Organism ◽  
Fruit Fly ◽  
In Vitro Assays ◽  
Behavioral Studies ◽  
And Behavior ◽  
Manual Manipulation

Abstract The fruit fly or Drosophila melanogaster has been used as a promising model organism in genetics, developmental and behavioral studies as well as in the fields of neuroscience, pharmacology, and toxicology. Not only all the developmental stages of Drosophila, including embryonic, larval, and adulthood stages, have been used in experimental in vivo biology, but also the organs, tissues, and cells extracted from this model have found applications in in vitro assays. However, the manual manipulation, cellular investigation and behavioral phenotyping techniques utilized in conventional Drosophila-based in vivo and in vitro assays are mostly time-consuming, labor-intensive, and low in throughput. Moreover, stimulation of the organism with external biological, chemical, or physical signals requires precision in signal delivery, while quantification of neural and behavioral phenotypes necessitates optical and physical accessibility to Drosophila. Recently, microfluidic and lab-on-a-chip devices have emerged as powerful tools to overcome these challenges. This review paper demonstrates the role of microfluidic technology in Drosophila studies with a focus on both in vivo and in vitro investigations. The reviewed microfluidic devices are categorized based on their applications to various stages of Drosophila development. We have emphasized technologies that were utilized for tissue- and behavior-based investigations. Furthermore, the challenges and future directions in Drosophila-on-a-chip research, and its integration with other advanced technologies, will be discussed.

Insight on the endothelialization of small silk-based tissue-engineered vascular grafts

2020 ◽  
Vol 43 (10) ◽  
pp. 631-644 ◽  
Author(s):  
Justine Cordelle ◽  
Sara Mantero
Keyword(s):  
Cell Adhesion ◽  
Vascular Tissue ◽  
Vascular Grafts ◽  
Small Diameter ◽  
Graft Patency ◽  
Ongoing Research ◽  
The Right ◽  
And Behavior

Along with an increased incidence of cardiovascular diseases, there is a strong need for small-diameter vascular grafts. Silk has been investigated as a biomaterial to develop such grafts thanks to different processing options. Endothelialization was shown to be extremely important to ensure graft patency and there is ongoing research on the development and behavior of endothelial cells on vascular tissue-engineered scaffolds. This article reviews the endothelialization of silk-based scaffolds processed throughout the years as silk non-woven nets, films, gel spun, electrospun, or woven scaffolds. Encouraging results were reported with these scaffolds both in vitro and in vivo when implanted in small- to middle-sized animals. The use of coatings and heparin or sulfur to enhance, respectively, cell adhesion and scaffold hemocompatibility is further presented. Bioreactors also showed their interest to improve cell adhesion and thus promoting in vitro pre-endothelialization of grafts even though they are still not systematically used. Finally, the importance of the animal models used to study the right mechanism of endothelialization is discussed.

scholarly journals Mg-Zn-Ca Alloys for Hemostasis Clips for Vessel Ligation: In Vitro and In Vivo Studies of Their Degradation and Response

Materials ◽  
2020 ◽  
Vol 13 (13) ◽  
pp. 3039 ◽  
Author(s):  
Yen-Hao Chang ◽  
Chun Chieh Tseng ◽  
Chih-Yeh Chao ◽  
Chung-Hwan Chen ◽  
Sung-Yen Lin ◽  
...  
Keyword(s):  
Degradation Rate ◽  
Protective Layer ◽  
Dip Coating ◽  
In Vivo Studies ◽  
Surface Measurement ◽  
In Vivo Experiments ◽  
Degradation Rates ◽  
And Behavior

To control the degradation rate of magnesium (Mg) alloys, chitosan (CHI) and L-glutamic acid (LGA) were used as coatings on Mg-Zn-Ca alloys via dip coating. In this study, either two or seven CHI/LGA layers were applied as a coating on Mg-2.8Zn-0.8Ca alloy (ZX31) and Mg-2.8Zn-0.8Ca hemostasis clips (ZX31 clips). The morphologies, compositions, and surface roughness of the specimens were characterized via scanning electron microscopy, Fourier transform infrared spectroscopy, and surface measurement devices. The degradation rates and behavior of the specimens were evaluated by immersing them in simulated body fluids and by applying these ZX31 clips on rabbits’ uterine tubes for five weeks. The specimen with seven layers (ZX31(CHI/LGA)7) exhibited improved corrosion behavior when compared with ZX31 or ZX31(CHI/LGA)2, with a reduced degradation rate of the Mg alloy in a simulated body environment. In vivo experiments showed that ZX31 clips exhibited good biocompatibilities in each group but could not maintain the clamping function for five weeks. The weight loss of ZX31(CHI/LGA)7 was significantly lower than that of the other groups. Consequently, it was verified that CHI can be used as a protective layer on a magnesium alloy surface via in vitro and in vivo experiments.

Hydrogen peroxide levels in mouse oocytes and early cleavage stage embryos developed in vitro or in vivo

Development ◽  
1990 ◽  
Vol 109 (2) ◽  
pp. 501-507 ◽  
Author(s):  
M.H. Nasr-Esfahani ◽  
J.R. Aitken ◽  
M.H. Johnson
Keyword(s):  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Cell Stage ◽  
Mouse Oocytes ◽  
Early Embryos ◽  
Individual Mouse ◽  
The Relationship ◽  
Developmental Block

We describe a fluorimetric method for measuring the level of H2O2 in individual mouse oocytes and early embryos. Levels of H2O2 are low but detectable in unfertilized oocytes recovered freshly from the female reproductive tract. The levels in early cleaving embryos (1-cell to 8-cell stages) immediately after recovery from the female tract seem to be slightly higher the later the stage examined. However, when embryos are cultured in vitro from the 1-cell or early 2-cell stage, H2O2 levels rise when the embryos reach the mid-2-cell stage and remain elevated until they enter the early 4-cell stage. No equivalent elevation of H2O2 is seen during the transition from 1-cell to 2-cell or from 4-cell to 8-cell stages. Embryos that are able to develop successfully in vitro, as well as those that show a developmental block at the 2-cell stage on culture in vitro, both show this rise in H2O2 levels after in vitro culture. The relationship between the rise in H2O2 and the ‘2-cell block’ to development is discussed.

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