A systematic review of the development and application of home cage monitoring in laboratory mice and rats.

BACKGROUND: Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. RESULTS: Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011-2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time periods (4-12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently. CONCLUSIONS: Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

A Pathophysiological Intersection of Diabetes and Alzheimer's Disease.

Diabetes is among the most prevalent diseases of the modern world and is strongly linked to an increased risk of numerous neurodegenerative disorders, although the exact pathophysiological mechanisms are not clear yet. Insulin resistance is a serious pathological condition, connecting type 2 diabetes, metabolic syndrome, and obesity. Recently, insulin resistance has been proven to be connected also to cognitive decline and dementias, including the most prevalent form, Alzheimer's disease. The relationship between diabetes and Alzheimer's disease regarding pathophysiology is so significant that it has been proposed that some presentations of the condition could be termed type 3 diabetes.

Protective Role of Mitochondrial Uncoupling Proteins against Age-Related Oxidative Stress in Type 2 Diabetes Mellitus.

The accumulation of oxidative damage to DNA and other biomolecules plays an important role in the etiology of aging and age-related diseases such as type 2 diabetes mellitus (T2D), atherosclerosis, and neurodegenerative disorders. Mitochondrial DNA (mtDNA) is especially sensitive to oxidative stress. Mitochondrial dysfunction resulting from the accumulation of mtDNA damage impairs normal cellular function and leads to a bioenergetic crisis that accelerates aging and associated diseases. Age-related mitochondrial dysfunction decreases ATP production, which directly affects insulin secretion by pancreatic beta cells and triggers the gradual development of the chronic metabolic dysfunction that characterizes T2D. At the same time, decreased glucose oxidation in skeletal muscle due to mitochondrial damage leads to prolonged postprandial blood glucose rise, which further worsens glucose homeostasis. ROS are not only highly reactive by-products of mitochondrial respiration capable of oxidizing DNA, proteins, and lipids but can also function as signaling and effector molecules in cell membranes mediating signal transduction and inflammation. Mitochondrial uncoupling proteins (UCPs) located in the inner mitochondrial membrane of various tissues can be activated by ROS to protect cells from mitochondrial damage. Mitochondrial UCPs facilitate the reflux of protons from the mitochondrial intermembrane space into the matrix, thereby dissipating the proton gradient required for oxidative phosphorylation. There are five known isoforms (UCP1-UCP5) of mitochondrial UCPs. UCP1 can indirectly reduce ROS formation by increasing glutathione levels, thermogenesis, and energy expenditure. In contrast, UCP2 and UCP3 regulate fatty acid metabolism and insulin secretion by beta cells and modulate insulin sensitivity. Understanding the functions of UCPs may play a critical role in developing pharmacological strategies to combat T2D. This review summarizes the current knowledge on the protective role of various UCP homologs against age-related oxidative stress in T2D.

Skeletal Muscle Uncoupling Proteins in Mice Models of Obesity.

Obesity and accompanying type 2 diabetes are among major and increasing worldwide problems that occur fundamentally due to excessive energy intake during its expenditure. Endotherms continuously consume a certain amount of energy to maintain core body temperature via thermogenic processes, mainly in brown adipose tissue and skeletal muscle. Skeletal muscle glucose utilization and heat production are significant and directly linked to body glucose homeostasis at rest, and especially during physical activity. However, this glucose balance is impaired in diabetic and obese states in humans and mice, and manifests as glucose resistance and altered muscle cell metabolism. Uncoupling proteins have a significant role in converting electrochemical energy into thermal energy without ATP generation. Different homologs of uncoupling proteins were identified, and their roles were linked to antioxidative activity and boosting glucose and lipid metabolism. From this perspective, uncoupling proteins were studied in correlation to the pathogenesis of diabetes and obesity and their possible treatments. Mice were extensively used as model organisms to study the physiology and pathophysiology of energy homeostasis. However, we should be aware of interstrain differences in mice models of obesity regarding thermogenesis and insulin resistance in skeletal muscles. Therefore, in this review, we gathered up-to-date knowledge on skeletal muscle uncoupling proteins and their effect on insulin sensitivity in mouse models of obesity and diabetes.

In Vitro Culturing of Adult Stem Cells: The Importance of Serum and Atmospheric Oxygen.

Adult stem cells are undifferentiated cells found in many different tissues in the adult human and animal body and are thought to be important for replacing damaged and dead cells during life. Due to their differentiation abilities, they have significant potential for regeneration and consequently therapeutic potential in various medical conditions. Studies on in vitro cultivation of different types of adult stem cells have shown that they have specific requirements for optimal proliferation and stemness maintenance as well as induced differentiation. The main factors affecting the success of stem cell cultivation are the composition of the growth medium, including the presence of serum, temperature, humidity, and contact with other cells and the composition of the atmosphere in which the cells grow. In this chapter, we review the literature and describe our own experience regarding the influence of the presence of fetal bovine serum in the medium and the oxygen concentration in the atmosphere on the stemness maintenance and survival of adult stem cells from various tissue sources such as adipose tissue, muscle, brain, and testicular tissue.

How early maternal deprivation changes the brain and behavior?

Early life stress can adversely influence brain development and reprogram brain function and consequently behavior in adult life. Adequate maternal care in early childhood is therefore particularly important for the normal brain development, and adverse early life experiences can lead to altered emotional, behavioral, and neuroendocrine stress responses in the adulthood. As a form of neonatal stress, maternal deprivation/separation is often used in behavioral studies to examine the effects of early life stress and for modeling the development of certain psychiatric disorders and brain pathologies in animal models. The temporary loss of maternal care during the critical postpartum periods remodels the offspring's brain and provokes long-term effects on learning and cognition, the development of mental disorders, aggression, and an increased tendency for the drug abuse. Early life stress through maternal deprivation affects neuroendocrine responses to stress in adolescence and adulthood by dysregulating the hypothalamic-pituitary-adrenal axis and permanently disrupts stress resilience. In this review, we focused on how improper maternal care during early postnatal life affects brain development resulting in modified behavior later in life.

Biogas production from brewery spent grain enhanced by bioaugmentation with hydrolytic anaerobic bacteria.

Lignocellulosic substrates are widely available but not easily applied in biogas production due to their poor anaerobic degradation. The effect of bioaugmentation by anaerobic hydrolytic bacteria on biogas production was determined by the biochemical methane potential assay. Microbial biomass from full scale upflow anaerobic sludge blanket reactor treating brewery wastewater was a source of active microorganisms and brewery spent grain a model lignocellulosic substrate. Ruminococcus flavefaciens 007C, Pseudobutyrivibrio xylanivorans Mz5(T), Fibrobacter succinogenes S85 and Clostridium cellulovorans as pure and mixed cultures were used to enhance the lignocellulose degradation and elevate the biogas production. P. xylanivorans Mz5(T) was the most successful in elevating methane production (+17.8%), followed by the coculture of P. xylanivorans Mz5(T) and F. succinogenes S85 (+6.9%) and the coculture of C. cellulovorans and F. succinogenes S85 (+4.9%). Changes in microbial community structure were detected by fingerprinting techniques.

Microbial community analyses in biogas reactors by molecular methods.

Successful biogas production is based on stable or adaptable microbial community structure and activity which depends on type of substrate used and several physico-chemical conditions in the bioreactor. Monitoring those and the dynamics of microbiota is important for planning and optimizing the biogas process, avoiding critical points and reaching the maximum methane yield. Methanogens are extremely difficult to study with culture-based methods. Molecular methods for microbial community structure analysis in biogas reactors, which offer qualitative and quantitative information on bacterial and archaeal species and their microbial community changes, and causes for process instability are surveyed in this review. For comparative studies semi-quantitative, rapid and cheap techniques like T-RFLP, DGGE and TGGE are used. More laborious and expensive techniques with high-throughput like semi-quantitative FISH and DNA microarrays and also quantitative techniques like qPCR and sequencing are used for phylogenetic analysis. Technique type adequacy for certain study depends on what information is needed and on several advantages and disadvantages every technique possesses.