Standardized and reproducible measurement of decision-making in mice

eLife, Journal Year: 2021, Volume and Issue: 10

Published: May 19, 2021

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern neuroscience, particularly for measurements of mouse behavior. Here, we show that task to probe decision-making mice produces reproducible multiple We adopted head-fixed perceptual value-based decision making, training protocol experimental hardware, software, procedures. trained 140 seven laboratories three countries, collected 5 million choices into publicly available database. Learning speed was variable laboratories, but once complete there were no significant differences behavior Mice different similar reliance on visual stimuli, past successes failures, estimates stimulus prior probability guide their choices. These reveal complex They establish standard rodent behavior, provide an unprecedented dataset open-access tools study mice. More generally, they indicate path toward achieving reproducibility neuroscience through collaborative open-science approaches.

Language: Английский

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Reliability of common mouse behavioural tests of anxiety: A systematic review and meta-analysis on the effects of anxiolytics

Neuroscience & Biobehavioral Reviews, Journal Year: 2022, Volume and Issue: 143, P. 104928 - 104928

Published: Oct. 30, 2022

The validity of widely used rodent behavioural tests anxiety has been questioned, as they often fail to produce consistent results across independent replicate studies. In this study, we assessed the sensitivity common in mice detect anxiolytic effects drugs prescribed treat humans. We conducted a pre-registered systematic review 814 studies reporting 25 compounds using for anxiety. Meta-analyses effect sizes treatments showed that only two out 17 commonly test measures reliably detected compounds. report considerable between-study variation size and even direction most anxiolytics on outcome variables. Our findings indicate general lack those cast serious doubt both construct predictive these tests. view scientifically valid ethically responsible research, call revision development more

Language: Английский

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Mass spectrometry‐based high‐throughput proteomics and its role in biomedical studies and systems biology

PROTEOMICS, Journal Year: 2022, Volume and Issue: 23(7-8)

Published: Nov. 9, 2022

Abstract There are multiple reasons why the next generation of biological and medical studies require increasing numbers samples. Biological systems dynamic, effect a perturbation depends on genetic background environment. As consequence, many conditions need to be considered reach generalizable conclusions. Moreover, human population clinical only sufficient statistical power if conducted at scale with precise measurement methods. Finally, proteins remain without functional annotations, because they have not been systematically studied under broad range conditions. In this review, we discuss latest technical developments in mass spectrometry (MS)‐based proteomics that facilitate large‐scale by fast efficient chromatography, scanning spectrometers, data‐independent acquisition (DIA), new software. We further highlight recent which demonstrate how high‐throughput (HT) can applied capture diversity, annotate gene functions or generate predictive prognostic models for diseases.

Language: Английский

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The Gut–Organ-Axis Concept: Advances the Application of Gut-on-Chip Technology

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 4089 - 4089

Published: Feb. 17, 2023

The intestine is considered to be a vital digestive organ absorb nutrients and the largest immune organ, while numerous microorganisms coexist with host. It well known that complex interactions between gut microbiota host’s system inevitably affect function of other organs, creating an “axis” them. During past few years, new technique based mainly on microfluidics cell biology has been developed emulate structure, function, microenvironment human gut, called “gut-on-chip”. This microfluidic chip provides insight into key aspects in health disease, such as gut–brain axis, gut–liver gut–kidney gut–lung axis. In this review, we first describe basic theory axis various composition parameter monitoring microarray systems, summarize development emerging advances gut–organ-on-chip, focus host-gut flora nutrient metabolism, highlight their role pathophysiological studies. addition, paper discusses challenges prospects for current further use gut–organ-on-chip platform.

Language: Английский

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Urine Excretion, Organ Distribution, and Placental Transfer of 6PPD and 6PPD-Quinone in Mice and Potential Developmental Toxicity through Nuclear Receptor Pathways

Environmental Science & Technology, Journal Year: 2023, Volume and Issue: 57(36), P. 13429 - 13438

Published: Aug. 29, 2023

The rubber antioxidant 6PPD has gained significant attention due to its highly toxic transformation product, 6PPD-quinone (6PPDQ). Despite their detection in urines of pregnant women, the placental transfer and developmental toxicity 6PPDQ are unknown. Here, we treated C57Bl/6 mice with 4 mg/kg or investigate urine excretion transfer. Female male exhibited sex difference profiles 6PPDQ. Urine concentrations were one order magnitude lower than those 6PPD, suggesting higher bioaccumulation In from embryonic day 11.5 15.5, showed ∼1.5–8 times placenta, embryo body, brain, Using vitro dual-luciferase reporter assays, revealed that activated human retinoic acid receptor α (RARα) retinoid X (RXRα) at as low 0.3 μM, which was ∼10-fold detected urines. RXRα 1.2 μM. These results demonstrate exposure risks during pregnancy emphasize need for further toxicological epidemiological investigations.

Language: Английский

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The (misleading) role of animal models in drug development

Frontiers in Drug Discovery, Journal Year: 2024, Volume and Issue: 4

Published: April 8, 2024

Animals like mice and rats have long been used in medical research to help understand disease test potential new treatments before human trials. However, while animal studies contributed important advances, too much reliance on models can also mislead drug development. This article explains for a general audience how is develop medicines, its benefits limitations, more accurate humane techniques—alternatives testing—could improve this process.

Language: Английский

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Improving reproducibility in animal research by splitting the study population into several ‘mini-experiments’

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Oct. 6, 2020

In light of the hotly discussed 'reproducibility crisis', a rethinking current methodologies appears essential. Implementing multi-laboratory designs has been shown to enhance external validity and hence reproducibility findings from animal research. We here aimed at proposing new experimental strategy that transfers this logic into single-laboratory setting. systematically introduced heterogeneity our study population by splitting an experiment several 'mini-experiments' spread over different time points few weeks apart. hypothesised observe improved in such 'mini-experiment' design comparison conventionally standardised design, according which all animals are tested one specific point time. By comparing both across independent replicates, we could indeed show use accurate detection exemplary treatment effects (behavioural physiological differences between four mouse strains) about half investigated strain comparisons. Thus, successfully implemented empirically validated easy-to-handle tackle poor studies. Since other experiments within life science disciplines share main characteristics with investigation reported here, these studies likely also benefit approach.

Language: Английский

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Proteomic and transcriptomic profiling reveal different aspects of aging in the kidney

eLife, Journal Year: 2021, Volume and Issue: 10

Published: March 9, 2021

Little is known about the molecular changes that take place in kidney during aging process. In order to better understand these changes, we measured mRNA and protein levels genetically diverse mice at different ages. We observed distinctive change as a function of age. Changes both are associated with increased immune infiltration decreases mitochondrial function. Proteins show greater extent reveal wide array biological processes including unique, organ-specific features kidney. Most importantly, functionally important age-related occur absence corresponding mRNA. Our findings suggest profiling alone provides an incomplete picture examination proteins essential not transcriptionally regulated.

Language: Английский

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Three Pillars of Automated Home-Cage Phenotyping of Mice: Novel Findings, Refinement, and Reproducibility Based on Literature and Experience

Frontiers in Behavioral Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Oct. 30, 2020

Animal models of neurodegenerative and neuropsychiatric disorders require extensive behavioral phenotyping. Currently, this presents several caveats the most important are: i) rodents are nocturnal animals, but mostly tested during light period; ii) conventional experiments take into consideration only a snapshot rich repertoire; iii) environmental factors as well experimenter influence often underestimated. Consequently, serious concerns have been expressed regarding reproducibility research findings on one hand, appropriate welfare animals (based principle 3Rs – reduce, refine replace) other hand. In order to address these problems improve behavioural phenotyping in general, solutions proposed developed. Undisturbed, 24/7 home-cage monitoring (HCM) is gaining increased attention popularity demonstrating potential substitute or complement methods by providing valuable data for identifying patterns that may missed otherwise. review, we will briefly describe different technologies used HCM systems. Thereafter, based our experience, focus two systems, IntelliCage (NewBehavior AG TSE-systems) Digital Ventilated Cage (DVC®, Tecniplast) how they developed applied recent years. Additionally, touch upon importance environmental/experimenter artifacts propose alternative suggestions performing published evidence. We discuss integration telemetry systems deriving certain physiological parameters can help description animal model offer better translation human studies. Ultimately, such be statistically interpreted analysed.

Language: Английский

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Sexual dimorphism in trait variability and its eco-evolutionary and statistical implications

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Nov. 17, 2020

Biomedical and clinical sciences are experiencing a renewed interest in the fact that males females differ many anatomic, physiological, behavioural traits. Sex differences trait variability, however, yet to receive similar recognition. In medical science, mammalian assumed have higher variability due estrous cycles (the ‘estrus-mediated hypothesis’); historically biomedical research, been excluded for this reason. Contrastingly, evolutionary theory associated data support ‘greater male hypothesis’. Here, we test these competing hypotheses 218 traits measured >26,900 mice, using meta-analysis methods. Neither hypothesis could universally explain patterns variability. bias was trait-dependent. While greater found morphological traits, were much more variable immunological Sex-specific has eco-evolutionary ramifications, including sex-dependent responses climate change, as well statistical implications power analysis considering sex difference variance.

Language: Английский

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