scholarly journals Behavioral Effects of Buspirone in Juvenile Zebrafish of Two Different Genetic Backgrounds

Toxics ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Amira Abozaid ◽  
Robert Gerlai

Anxiety continues to represent a major unmet medical need. Despite the availability of numerous anxiolytic drugs, a large proportion of patients do not respond well to current pharmacotherapy, or their response diminishes with chronic drug application. To discover novel compounds and to investigate the mode of action of anxiolytic drugs, animal models have been proposed. The zebrafish is a novel animal model in this research. It is particularly appropriate, as it has evolutionarily conserved features, and drug administration can be employed in a non-invasive manner by immersing the fish into the drug solution. The first step in the analysis of anxiolytic drugs with zebrafish is to test reference compounds. Here, we investigate the effects of buspirone hydrochloride, an anxiolytic drug often employed in the human clinic. We utilize two genetically distinct populations of zebrafish, ABSK, derived from the quasi-inbred AB strain, and WT, a genetically heterogeneous wild-type population. We placed juvenile (10–13-day, post-fertilization, old) zebrafish singly in petri dishes containing one of four buspirone concentrations (0 mg/L control, 5 mg/L, 20 mg/L or 80 mg/L) for 1 h, with each fish receiving a single exposure to one concentration, a between subject experimental design. Subsequently, we recorded the behavior of the zebrafish for 30 min using video-tracking. Buspirone decreased distance moved, number of immobility episodes and thigmotaxis, and it increased immobility duration and turn angle in a quasi-linear dose dependent but genotype independent manner. Although it is unclear whether these changes represent anxiolysis in zebrafish, the results demonstrate that behavioral analysis of juvenile zebrafish may be a sensitive and simple way to quantify the effects of human anxiolytic drugs.

2019 ◽  
Vol 47 (20) ◽  
pp. 10881-10893 ◽  
Author(s):  
Marco Nousch ◽  
Assa Yeroslaviz ◽  
Christian R Eckmann

Abstract RNA-modifying enzymes targeting mRNA poly(A) tails are universal regulators of post-transcriptional gene expression programs. Current data suggest that an RNA-binding protein (RBP) directed tug-of-war between tail shortening and re-elongating enzymes operates in the cytoplasm to repress or activate specific mRNA targets. While this concept is widely accepted, it was primarily described in the final meiotic stages of frog oogenesis and relies molecularly on a single class of RBPs, i.e. CPEBs, the deadenylase PARN and cytoplasmic poly(A) polymerase GLD-2. Using the spatial and temporal resolution of female gametogenesis in the nematode C. elegans, we determined the distinct roles of known deadenylases throughout germ cell development and discovered that the Ccr4–Not complex is the main antagonist to GLD-2-mediated mRNA regulation. We find that the Ccr4–Not/GLD-2 balance is critical for essentially all steps of oocyte production and reiteratively employed by various classes of RBPs. Interestingly, its two deadenylase subunits appear to affect mRNAs stage specifically: while a Caf1/GLD-2 antagonism regulates mRNA abundance during all stages of oocyte production, a Ccr4/GLD-2 antagonism regulates oogenesis in an mRNA abundance independent manner. Our combined data suggests that the Ccr4–Not complex represents the evolutionarily conserved molecular opponent to GLD-2 providing an antagonistic framework of gene-specific poly(A)-tail regulation.


2021 ◽  
Author(s):  
Naihua Natalie Gong ◽  
An H Dang ◽  
Benjamin Mainwaring ◽  
Emily Shields ◽  
Karl Schmeckpeper ◽  
...  

The maturation of sleep behavior across a lifespan (sleep ontogeny) is an evolutionarily conserved phenomenon. Mammalian studies have shown that in addition to increased sleep duration, early life sleep exhibits stark differences compared to mature sleep with regard to the amount of time spent in certain sleep states. How intrinsic maturation of sleep output circuits contributes to sleep ontogeny is poorly understood. The fruit fly Drosophila melanogaster exhibits multifaceted changes to sleep from juvenile to mature adulthood. Here, we use a non-invasive probabilistic approach to investigate changes in sleep architecture in juvenile and mature flies. Increased sleep in juvenile flies is driven primarily by a decreased probability of transitioning to wake, and characterized by more time in deeper sleep states. Functional manipulations of sleep-promoting neurons in the dFB suggest these neurons differentially regulate sleep in juvenile and mature flies. Transcriptomic analysis of dFB neurons at different ages and a subsequent RNAi screen implicate genes involved in distinct molecular processes in sleep control of juvenile and mature flies. These results reveal that dynamic transcriptional states of sleep output neurons contribute to changes in sleep across the lifespan.


2021 ◽  
Author(s):  
Revathi Balasubramanian ◽  
Xuanyu Min ◽  
Peter M.J. Quinn ◽  
Quentin Lo Giudice ◽  
Chenqi Tao ◽  
...  

The developing vertebrate eye cup is partitioned into the neural retina (NR), the retinal pigmented epithelium (RPE) and the ciliary margin (CM). By single cell analysis, we showed that a gradient of FGF signaling regulates demarcation and subdivision of the CM and controls its stem cell-like property of self-renewal, differentiation and survival. This regulation by FGF is balanced by an evolutionarily conserved Wnt signaling gradient induced by the lens ectoderm and the periocular mesenchyme, which specifies the CM and the distal RPE. These two morphogen gradients converge in the CM where FGF signaling promotes Wnt signaling by stabilizing β-catenin in a GSK3β-independent manner. We further showed that activation of Wnt signaling converts the NR to either the CM or the RPE depending on the level of FGF signaling. Conversely, activation of FGF transforms the RPE to the NR or CM dependent on Wnt activity. We demonstrated that the default fate of the eye cup is the NR, but synergistic FGF and Wnt signaling promotes CM formation both in vivo and in retinal organoid culture of human iPS cells. Our study reveals that the vertebrate eye develops through phase transition determined by a combinatorial code of FGF and Wnt signaling.


Author(s):  
Nashwan Saleh Mohammed Al-ashwal

Aim: This study is really aimed to explain the possibility of viewing the coronary arteries by transthoracic echocardiography and its importance in taking the diagnosis about non-specific chest discomfort like tightness or burning with back pain and others, to help patients &   save their lives. Presentation: 40 years old male complains  of  intermittent recurrent chest tightness and back pain for 6 months ago , and had a non-specific electrocardiogram and normal echocardiogram findings, with hypertension of 160/98 mmHg discovered on the first visit to see a doctor that prescribed for him bisoprolol 5 mg tab  per day and anxiolytic drugs , and while he was using these medicines  he was suffered from new recurrence, therefore, echocardiogram examination for coronary arteries was done and revealed its walls thickening and stenosis. Conclusion: the conclusion of this study are revealing the transthoracic echocardiogram as a valuable non-invasive imaging technic for examination of the coronary arteries with clear detection of the walls thickening and lumens diameters, and it will contribute to putting a prevention plans for decreasing the myocardial infarctions and its complications.


2021 ◽  
Author(s):  
E Emilie Cardona ◽  
C Cervin Guyomar ◽  
Thomas Desvignes ◽  
J Jérôme Montfort ◽  
Samia Guendouz ◽  
...  

AbstractCirculating miRNAs (c-miRNAs) are found in most, if not all, biological fluids and are becoming well established biomarkers of many human pathologies. The aim of the present study was to investigate the potential of c-miRNAs as biomarkers of reproductive and metabolic states in fish, a question that has received little attention. Plasma was collected throughout the reproductive cycle from rainbow trout females subjected to two different feeding levels to trigger contrasting metabolic states; ovarian fluid was sample at ovulation. Fluid samples were subjected to small RNA-seq analysis followed by quantitative PCR validation for a subset of promising c-miRNA biomarkers. A comprehensive miRNA repertoire, which was lacking in trout, was first established to allow subsequent analysis. We first showed that biological fluids miRNAomes are complex and encompass a high proportion of the overall species miRNAome. While sharing a high proportion of common miRNAs, plasma and ovarian fluid miRNAomes exhibited strong fluid-specific signatures. We further showed that the plasma miRNAome exhibited major significant changes depending on metabolic and reproductive state. We subsequently identified three (miR-1-1/2-3p, miR-133-a-1/2-3p and miR-206-3p) evolutionarily conserved muscle-specific miRNA that accumulate in the plasma in response to high feeding rates, making these myomiRs strong candidate biomarkers of active myogenesis. We also identified miR-202-5p as a candidate biomarker for reproductive success that could be used to predict ovulation and/or egg quality. These highly promising results reveal the high potential of c-miRNAs as physiologically relevant biomarkers and pave the way for the use of c-miRNAs for non-invasive phenotyping in various fish species.


2019 ◽  
Vol 38 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Monamie Ringhofer ◽  
Clark Kendrick Go ◽  
Sota Inoue ◽  
Renata S. Mendonça ◽  
Satoshi Hirata ◽  
...  

AbstractIn animal groups, individual interactions achieve coordinated movements to maintain cohesion. In horse harem groups, herding is a behavior in which males chase females from behind; it is considered to assist with group cohesiveness. However, the mechanisms by which the individuals move to maintain group cohesion are unknown. We applied novel non-invasive methods of drone filming and video tracking to observe horse movements in the field with high temporal and spatial resolution. We tracked all group members and drew trajectories. We analyzed the movements of females and found two phases of interactions based on their timing of movement initiation. The females that moved first were those nearest to the herding male, while the movement initiation of the later females was determined by the distance from the nearest moving female, not by the distance from the herding male. These interactions are unique among animal group movements and might represent a herding mechanism responsible for maintaining group cohesion. This might be due to long-term stable relationships within a harem group and strong social bonds between females. This study showed that the combination of drone filming and video tracking is a useful method for analyzing the movements of animals simultaneously in high resolution.


2012 ◽  
Vol 393 (6) ◽  
pp. 429-439 ◽  
Author(s):  
Cletus Cheyuo ◽  
Weng-Lang Yang ◽  
Ping Wang

Abstract Chronic neurodegenerative disorders and acute injuries of the central nervous system exert a prohibitive economic burden, which is aggravated by an unmet medical need for the development of effective neurotherapeutics. The evolutionarily conserved neuropeptide, adrenomedullin (AM), and its binding protein, AMBP-1, also known as complement factor H, play important roles in brain physiology, and their expression is altered in brain pathology. In this review, we discuss the molecular regulation of AM and AMBP-1 and the pivotal roles they play in neuroprotection following brain injury. We assess the reciprocal synergistic effects of AM and AMBP-1 and make suggestions for the design of a novel combination neurotherapy devoid of the potential hypotensive effects of AM while optimizing its neuroprotective property.


Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 411
Author(s):  
Rebecca A. Dewhirst ◽  
Joseph Lei ◽  
Cassandra A. Afseth ◽  
Cristina Castanha ◽  
Christina M. Wistrom ◽  
...  

Upregulation of acetate fermentation in plants has recently been described as an evolutionarily conserved drought survival strategy, with the amount of acetate produced directly correlating to survival. However, destructive measurements are required to evaluate acetate-linked drought responses, limiting the temporal and spatial scales that can be studied. Here, 13C-labeling studies with poplar (Populus trichocarpa) branches confirmed that methyl acetate is produced in plants from the acetate-linked acetylation of methanol. Methyl acetate emissions from detached leaves were strongly stimulated during desiccation, with total emissions decreasing with the leaf developmental stage. In addition, diurnal methyl acetate emissions from whole physiologically active poplar branches increased as a function of temperature, and light-dark transitions resulted in significant emission bursts lasting several hours. During experimental drought treatments of potted poplar saplings, light-dark methyl acetate emission bursts were eliminated while strong enhancements in methyl acetate emissions lasting > 6 days were observed with their initiation coinciding with the suppression of transpiration and photosynthesis. The results suggest that methyl acetate emissions represent a novel non-invasive tracer of acetate-mediated temperature and drought survival response in plants. The findings may have important implications for the future understanding of acetate-mediated drought responses to transcription, cellular metabolism, and hormone signaling, as well as its associated changes in carbon cycling and water use from individual plants to whole ecosystems.


2021 ◽  
Vol 118 (15) ◽  
pp. e2022887118
Author(s):  
Jan Fabio Nickels ◽  
Ashleigh Katrine Edwards ◽  
Sebastian Jespersen Charlton ◽  
Amanda Møller Mortensen ◽  
Sif Christine Lykke Hougaard ◽  
...  

Methylation of histone H3K9 is a hallmark of epigenetic silencing in eukaryotes. Nucleosome modifications often rely on positive feedback where enzymes are recruited by modified nucleosomes. A combination of local and global feedbacks has been proposed to account for some dynamic properties of heterochromatin, but the range at which the global feedbacks operate and the exact mode of heterochromatin propagation are not known. We investigated these questions in fission yeast. Guided by mathematical modeling, we incrementally increased the size of the mating-type region and profiled heterochromatin establishment over time. We observed exponential decays in the proportion of cells with active reporters, with rates that decreased with domain size. Establishment periods varied from a few generations in wild type to >200 generations in the longest region examined, and highly correlated silencing of two reporters located outside the nucleation center was observed. On a chromatin level, this indicates that individual regions are silenced in sudden bursts. Mathematical modeling accounts for these bursts if heterochromatic nucleosomes facilitate a deacetylation or methylation reaction at long range, in a distance-independent manner. A likely effector of three-dimensional interactions is the evolutionarily conserved Swi6HP1 H3K9me reader, indicating the bursting behavior might be a general mode of heterochromatin propagation.


BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Emilie Cardona ◽  
Cervin Guyomar ◽  
Thomas Desvignes ◽  
Jérôme Montfort ◽  
Samia Guendouz ◽  
...  

Abstract Background Circulating miRNAs (c-miRNAs) are found in most, if not all, biological fluids and are becoming well-established non-invasive biomarkers of many human pathologies. However, their features in non-pathological contexts and whether their expression profiles reflect normal life history events have received little attention, especially in non-mammalian species. The aim of the present study was to investigate the potential of c-miRNAs to serve as biomarkers of reproductive and metabolic states in fish. Results The blood plasma was sampled throughout the reproductive cycle of female rainbow trout subjected to two different feeding regimes that triggered contrasting metabolic states. In addition, ovarian fluid was sampled at ovulation, and all samples were subjected to small RNA-seq analysis, leading to the establishment of a comprehensive miRNA repertoire (i.e., miRNAome) and enabling subsequent comparative analyses to a panel of RNA-seq libraries from a wide variety of tissues and organs. We showed that biological fluid miRNAomes are complex and encompass a high proportion of the overall rainbow trout miRNAome. While sharing a high proportion of common miRNAs, the blood plasma and ovarian fluid miRNAomes exhibited strong fluid-specific signatures. We further revealed that the blood plasma miRNAome significantly changed depending on metabolic and reproductive states. We subsequently identified three evolutionarily conserved muscle-specific miRNAs or myomiRs (miR-1-1/2-3p, miR-133a-1/2-3p, and miR-206-3p) that accumulated in the blood plasma in response to high feeding rates, making these myomiRs strong candidate biomarkers of active myogenesis. We also identified miR-202-5p as a candidate biomarker for reproductive success that could be used to predict ovulation and/or egg quality. Conclusions Together, these promising results reveal the high potential of c-miRNAs, including evolutionarily conserved myomiRs, as physiologically relevant biomarker candidates and pave the way for the use of c-miRNAs for non-invasive phenotyping in various fish species.


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