Ilar Journal最新文献

Review of the use of nonexperimental xenobiotics in terrestrial animal models and the potential unintended consequences of these compounds, including drug-related side effects and adverse reactions.

As mentioned in other chapters, reproducibility of research data is very complicated and has numerous contributors for concerns. This chapter will discuss the animal housing systems and corresponding husbandry practices in regard to current practices and known and potential confounders in the research environment. This area has a very high impact for reproducibility and comparability of study data outcomes.

The use of animal models remains critical in preclinical and translational research. The reliability of the animal models and aspects of their validity is likely key to effective translation of findings to medicine. However, despite considerable uniformity in animal models brought about by control of genetics, there remain a number of social as well as innate and acquired behavioral characteristics of laboratory animals that may impact on research outcomes. These include the effects of strain and genetics, age and development, sex, personality and affective states, and social factors largely brought about by housing and husbandry. In addition, aspects of the testing environment may also influence research findings. A number of considerations resulting from the animals' innate and acquired behavioral characteristics as well as their social structures are described. Suggestions for minimizing the impact of these factors on research are provided.

The use of aquatic animals in ecotoxicology, genetic, and biomedical research has grown immensely in recent years, especially due to the increased use of zebrafish in the laboratory setting. Because water is the primary environment of most aquatic species, the composition and management of this water is paramount to ensuring their health and welfare. In this publication, we will describe the important variables in water quality that can influence animal health and research results, using the zebrafish model for detailed specifics of optimal conditions. Wherever possible, recommendations are provided to reduce the potential impact of poor or highly variable water quality, and standards are given which can be used as institutional goals to maximize animal health and welfare and reduce research variability. It is increasingly important that authors of publications describing work done using aquatic models characterize water quality and other environmental conditions of the animal environment so that the work can be repeated and understood in context of these important factors. It is clear that there are a great many extrinsic factors which may influence research outcomes in the aquatics model laboratory setting, and consequently, an increased level of funding will be essential to support continued research exploring these and other important husbandry conditions. References from a large body of literature on this subject are provided.

Sound and vibration have been shown to alter animal behavior and induce physiological changes as well as to cause effects at the cellular and molecular level. For these reasons, both environmental factors have a considerable potential to alter research outcomes when the outcome of the study is dependent on the animal existing in a normal or predictable biological state. Determining the specific levels of sound or vibration that will alter research is complex, as species will respond to different frequencies and have varying frequencies where they are most sensitive. In consideration of the potential of these factors to alter research, a thorough review of the literature and the conditions that likely exist in the research facility should occur specific to each research study. This review will summarize the fundamental physical properties of sound and vibration in relation to deriving maximal level standards, consider the sources of exposure, review the effects on animals, and discuss means by which the adverse effects of these factors can be mitigated.

Light is a key extrinsic factor to be considered in operations and design of animal room facilities. Over the past four decades, many studies on typical laboratory animal populations have demonstrated impacts on neuroendocrine, neurobehavioral, and circadian physiology. These effects are regulated independently from the defined physiology for the visual system. The range of physiological responses that oscillate with the 24 hour rhythm of the day include sleep and wakefulness, body temperature, hormonal secretion, and a wide range of other physiological parameters. Melatonin has been the chief neuroendocrine hormone studied, but acute light-induced effects on corticosterone as well as other hormones have also been observed. Within the last two decades, a new photosensory system in the mammalian eye has been discovered. A small set of retinal ganglion cells, previously thought to function as a visual output neuron, have been shown to be directly photosensitive and act differently from the classic photoreceptors of the visual system. Understanding the effects of light on mammalian physiology and behavior must take into account how the classical visual photoreceptors and the newly discovered ipRGC photoreceptor systems interact. Scientists and facility managers need to appreciate lighting impacts on circadian, neuroendocrine, and neurobehavioral regulation in order to improve lighting of laboratory facilities to foster optimum health and well-being of animals.

Environmental variables can have profound effects on the biological responses of research animals and the outcomes of experiments dependent on them. Some of these influences are both predictable and unpredictable in effect, many are challenging to standardize, and all are influenced by the planning and conduct of experiments and the design and operation of the vivarium. Others are not yet known. Within the immediate environment where the research animal resides, in the vivarium and in transit, the most notable of these factors are ambient temperature, relative humidity, gaseous pollutant by-products of animal metabolism and physiology, dust and particulates, barometric pressure, electromagnetic fields, and illumination. Ambient temperatures in the animal housing environment, in particular those experienced by rodents below the thermoneutral zone, may introduce degrees of stress and thermoregulatory compensative responses that may complicate or invalidate study measurements across a broad array of disciplines. Other factors may have more subtle and specific effects. It is incumbent on scientists designing and executing experiments and staff responsible for animal husbandry to be aware of, understand, measure, systematically record, control, and account for the impact of these factors on sensitive animal model systems to ensure the quality and reproducibility of scientific studies.

Our bodies and those of our animal research subjects are colonized by bacterial communities that occupy virtually every organ system, including many previously considered sterile. These bacteria reside as complex communities that are collectively referred to as microbiota. Prior to the turn of the century, characterization of these communities was limited by a reliance on culture of organisms on a battery of selective media. It was recognized that the vast majority of microbes, especially those occupying unique niches of the body such as the anaerobic environment of the intestinal tract, were uncultivatable. However, with the onset and advancement of next-generation sequencing technology, we are now capable of characterizing these complex communities without the need to cultivate, and this has resulted in an explosion of information and new challenges in interpreting data generated about, and in the context of, these complex communities. We have long known that these microbial communities often exist in an intricate balance that, if disrupted (ie, dysbiosis), can lead to disease or increased susceptibility to disease. Because of many functional redundancies, the makeup of these colonies can vary dramatically within healthy individuals [1]. However, there is growing evidence that subtle differences can alter the phenotype of various animal models, which may translate to the varying susceptibility to disease seen in the human population. In this manuscript, we discuss how to include complex microbiota as a consideration in experimental design and model reproducibility and how to exploit the extensive variation that exists in contemporary rodent research colonies. Our focus will be the intestinal or gut microbiota (GM), but it should be recognized that microbial communities exist in many other body compartments and these too likely influence health and disease [2, 3]. Much like host genetics, can we one day harness the vast genetic capacity of the microbes we live with in ways that will benefit human and animal health?

Feed plays a central role in the physiological development of terrestrial and aquatic animals. Historically, the feeding practice of aquatic research species derived from aquaculture, farmed, or ornamental trades. These diets are highly variable, with limited quality control, and have been typically selected to provide the fastest growth or highest fecundity. These variations of quality and composition of diets may affect animal/colony health and can introduce confounding experimental variables into animal-based studies that impact research reproducibility.