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The activation of autonomic and hypothalamo-pituitary-adrenal (HPA) systems occurs interdependently with behavioral adjustments under varying environmental demands. Nevertheless, laboratory rodent studies examining the neural bases of stress responses have generally attributed increments in these systems to be monolithic, regardless of whether an active or passive coping strategy is employed. Using the shock probe defensive burying test (SPDB) to measure stress-coping features naturalistically in male and female rats, we identify a neural pathway whereby activity changes may promote distinctive response patterns of hemodynamic and HPA indices typifying active and passive coping phenotypes. Optogenetic excitation of the rostral medial prefrontal cortex (mPFC) input to the ventrolateral periaqueductal gray (vlPAG) decreased passive behavior (immobility), attenuated the glucocorticoid hormone response, but did not prevent arterial pressure and heart rate increases associated with rats' active behavioral (defensive burying) engagement during the SPDB. In contrast, inhibition of the same pathway increased behavioral immobility and attenuated hemodynamic output but did not affect glucocorticoid increases. Further analyses confirmed that hemodynamic increments occurred preferentially during active behaviors and decrements during immobility epochs, whereas pathway manipulations, regardless of the directionality of effect, weakened these correlational relationships. Finally, neuroanatomical evidence indicated that the influence of the rostral mPFC→vlPAG pathway on coping response patterns is mediated predominantly through GABAergic neurons within vlPAG. These data highlight the importance of this prefrontal→midbrain connection in organizing stress-coping responses and in coordinating bodily systems with behavioral output for adaptation to aversive experiences. [ABSTRACT FROM AUTHOR]

Social isolation affects the brain and behavior in a variety of animals, including humans. Studies in traditional laboratory rodents, including mice and rats, have supported the idea that short-term social isolation promotes affiliative social behaviors, while long-term isolation promotes anti-social behaviors, including increased aggression. Whether the effects of isolation on the social behaviors of mice and rats generalize to other rodents remains understudied. In the current study, we characterized the effects of short-term (3-days) social isolation on the social behaviors of adult prairie voles (Microtus ochrogaster) during same-sex and opposite-sex social interactions. Our experiments revealed that short-term isolation did not affect rates of ultrasonic vocalizations or time spent in non-aggressive social behaviors and huddling during same-sex and opposite-sex interactions. Unexpectedly, although short-term isolation also did not affect time spent in resident-initiated and mutually-initiated aggressive behavior, we found that short-term isolation increased time spent in visitor-initiated aggression during male-male interactions. Our findings highlight the importance of comparative work across species and the consideration of social context to understand the diverse ways in which social isolation can impact social behavior. [ABSTRACT FROM AUTHOR]

Background: The bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear. Aim: The present study investigated the effects on the BNST neurochemical composition and neuronal structure in critical moments of the postnatal period in gestational protein-restricted male rats' offspring. Methods: Dams were maintained during the pregnancy on isocaloric rodent laboratory chow with standard protein content [NP, 17%] or low protein content [LP, 6%]. BNST from male NP and age-matched LP offspring was studied using the isotropic fractionator method, Neuronal 3D reconstruction, dendritic-tree analysis, blotting analysis, and high-performance liquid chromatography. Results: Serum corticosterone levels were higher in male LP offspring than NP rats in 14-day-old offspring, without any difference in 7-day-old progeny. The BNST total cell number and anterodorsal BNST division volume in LP progeny were significantly reduced on the 14th postnatal day compared with NP offspring. The BNST HPLC analysis from 7 days-old LP revealed increased norepinephrine levels compared to NP progeny. The BNST blot analysis from 7-day-old LP revealed reduced levels of GR and BDNF associated with enhanced CRF1 expression compared to NP offspring. 14-day-old LP offspring showed reduced expression of MR and 5HT1A associated with decreased DOPAC and DOPA turnover levels relative to NP rats. In Conclusion, the BNST cellular and neurochemical changes may represent adaptation during development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition alters the BNST content and structure and contributes to already-known behavioral changes. [ABSTRACT FROM AUTHOR]

Early life experiences can have lasting impacts on an animal's development. Extensive research evidence aligns across both human and non-human rodent and primate laboratory animals showing negative impacts of early life adversity such as impairments in neurological and behavioural development. Farmed animals experience a range of adversities across their production lifetimes, often early in life, including species atypical social groupings, invasive husbandry procedures, and transport. Correspondingly, farmed animals also demonstrate a wide range of impairments such as stereotypic, injurious, and other abnormal behaviours. An individual, however, needs to experience adversity to be able to develop resilience and coping mechanisms that facilitate dealing with challenges later in life. Not all individuals will experience stress vulnerability following adversity, with some individuals instead developing stress resilience. This mini review collates evidence on the positive effects of early life adversity on improving adaptability in farmed species, both terrestrial and aquatic. While evidence across farmed animal species is currently much less than for humans, laboratory rodents or non-human primates, similar patterns emerge where mild adversity early in life, can improve the adaptability of the animal in the face of future stressors. Many views of optimised welfare posit that farmed animals should be housed in as natural environments as possible to limit many of the typical adversities they face. However, strategic mild exposure to early life adversity may facilitate improved animal welfare under intensive commercial farming conditions. Future research into this area could provide management tools to better predict and promote stress resilience over stress vulnerability. [ABSTRACT FROM AUTHOR]

Introduction: Surgical interventions in mice require appropriate pain relief to ensure animal welfare and to avoid influence of pain on research findings. Carprofen is a non-steroidal anti-inflammatory drug commonly used as an analgesic for interventions inducingmild tomoderate pain in laboratory rodents. Despite its frequent use, species-specific data on pharmacokinetics (PK), side effects, and potential impact on behavioral pain indicators are limited. Methods: We determined PK and tolerability profiles of carprofen in healthy male and female C57BL/6Jmice (n = 42), administered at highest recommended doses via single subcutaneous (s.c.) injection (20 mg/kg) and oral self-administration (25 mg/kg/24 h) per drinking water (d.w.) for 5 days. Plasma concentrations were measured at various time points after the start of the treatment (n = 6 per time point), and side effects were evaluated using amodified Irwin test battery, hematology, and histopathology. Additionally, potential interference with cage-side behaviors commonly used for pain assessment, such as the mouse grimace scale, wheel running, burrowing, nesting, and grooming activity, was investigated. Results: Maximum plasma concentrations of 133.4 ± 11.3µg/ml were reached 1 h after single s.c. injection with an elimination half-life of 8.52 h. Intake from d.w. resulted in a steady state within 24 h after the start of the treatment with plasma levels of around 60µg/ml over 5 days in both sexes. The medicated water was well-accepted, and increased d.w. intake was observed in the first 24 h after exposure (p < 0.0001). The Irwin test revealed only minor influence on tested behavior and physiological functions. However, during treatment via d.w., an increase in body temperature (p < 0.0001) was observed, as well as a reduction in voluntary wheel running activity by 49-70% inmalemice. Moreover, grooming behavior was slightly affected. Hematology and histopathology were without pathological findings that could be attributed to carprofen treatment. High-dose carprofen can be considered safe and of favorable PK for both administration routes assessed in healthy C57BL/6J mice of both sexes. Further efficacy evaluation of carprofen as monoanalgesic or component of multimodal post-surgical regimens is clearly encouraged; however, the impact on behavioral markers used for pain assessment should be considered in this context. [ABSTRACT FROM AUTHOR]

Aims: Cardiovascular disease is the primary cause of mortality and morbidity, and its terminal phase is chronic heart failure. The present study aimed to examine the protective impact of rosuvastatin on isoproterenol-induced chronic heart failure and investigate plausible related mechanisms. Rosuvastatin, a drug with multiple pleiotropic properties, has been examined for its cardioprotective effects in heart failure induced by isoproterenol. Methods: Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure by subcutaneous injection. Simultaneously, rosuvastatin (10 mg/kg) was orally administrated from day 1 to day 14. Protective effects were evaluated by heart grading and gross morphology, hemodynamic parameter, cardiac troponin I, heart mitochondrial enzyme and lysosomal hydrolases and pro inflammatory cytokines levels were analyzed. Results: Rosuvastatin (10 mg/kg) significantly attenuated isoproterenol-induced hypertrophy, remodeling and dysfunction of the ventricle, reduced the heart mitochondrial enzyme and lysosomal hydrolases and normalized the increased hemodynamic and pro inflammatory cytokines levels. Conclusions: The study highlights the preventive effects of, rosuvastatin, against heart failure. The results of the research indicate that rosuvastatin has cardioprotective effects on the experimental model, which were supported by several characteristics. However, further research is required to identify the precise molecular mechanisms and signalling pathways of rosuvastatin's impact on heart failure. [ABSTRACT FROM AUTHOR]

Background/Objectives: Intratracheal administration of bleomycin (BLM) to laboratory rodents is a standard, widely used technique used to model pulmonary fibrosis (PF). BLM, as a modeling agent, is produced mainly in the form of two salts—sulfate and chloride. We compared the results of modeling PF in SD rats by intratracheal administration of BLM sulfate and BLM chloride. Methods: Healthy mature male SD rats were used. PF was modeled by intratracheal administration of BLM sulfate and BLM chloride at a dose of 3 mg/kg. The criteria for the development of PF included body weight gain, changes in respiratory parameters, relative lung weight, cellular composition of broncho-alveolar fluid (BALF), histological assessment of the severity of PF with trichrome Masson staining. Results: Intratracheal administration of both BLM salts led to the development of pronounced PF, which was determined by changes in all of the measured parameters relative to control animals. There were no significant differences between the BLM sulfate and BLM chloride groups in body weight gain, hydroxyproline content, and histological evaluation. However, significant differences were identified in the cellular composition of BALF—a significant increase in alveolar macrophages and neutrophils levels in animals treated with BLM sulfate. Conclusions: Intratracheal administration of both BLM salts led to the development of severe PF; however, the inflammatory process in animals receiving BLM sulfate was more pronounced and prolonged than in animals receiving BLM chloride, which in the former, when observed more than 21 days after modeling, can lead to more severe PF. [ABSTRACT FROM AUTHOR]

Abstract Background Dihydrogen (H2) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates. Over the past few years, numerous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts, making the characterization of its production in laboratory species of major preclinical importance. Methods This study proposes an innovative solution to accurately monitor H2 production in free‐moving rodents while respecting animal welfare standards. The developed device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained, and the H2 concentration was continuously analyzed. After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked, tests were carried out on rats and mice with different metabolic phenotypes, over 12 min to 1‐h experiments and repeatedly. H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first‐order moving average. Results HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats, respectively, 2.64 and 1.27 nmol.s−1 per animal. In addition, the ingestion of inulin, a dietary fiber, stimulated H2 production in mice. HPRs were 0.46 nmol.s−1 for animals under control diet and 1.99 nmol.s−1 for animals under inulin diet. Conclusions The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.

This article examines the care of rodents in laboratory animal research, highlighting the historical and current use of rodents in research and the concept of a "culture of care" within research facilities. It emphasizes the need for comprehensive veterinary assessment and expertise in rodent care, as well as the importance of interdisciplinary collaboration and dialogue in advancing the principles of replacement, reduction, and refinement in animal research. The article also discusses public engagement with animal research and the role of social sciences and humanities in understanding care practices. It concludes by emphasizing the importance of institutional organization and logistics in promoting good animal care. [Extracted from the article]

We studied psychoemotional characteristics and the blood level of corticosterone in sexually mature male C57BL/6 mice (n=40): intact (control), after simulating preoperative stress and surgery, after surgery, and after anesthesia alone. It was found that the anxiety index calculated on the basis of testing in the elevated plus maze was significantly higher in both groups of operated animals. The mice of both operated groups and animals exposed to anesthesia alone showed increased anxiety. Symptoms indicating a high probability of transition of anxiety into a psychoemotional disorder have been recorded. [ABSTRACT FROM AUTHOR]

• Rodent grooming is an important key behavior. • The study analyzed mouse genes linked to aberrant hetero-grooming behavior. • The genes formed a molecular network with several gene clusters. • They can help clarify mechanisms of rodent grooming behavior. Highly prevalent in laboratory rodents, 'social' hetero-grooming behavior is translationally relevant to modeling a wide range of neuropsychiatric disorders. Here, we comprehensively evaluated all known to date mouse genes linked to aberrant hetero-grooming phenotype, and applied bioinformatics tools to construct a network of their established protein–protein interactions (PPI). We next identified several distinct molecular clusters within this complex network, including neuronal differentiation, cytoskeletal, WNT-signaling and synapsins-associated pathways. Using additional bioinformatics analyses, we further identified 'central' (hub) proteins within these molecular clusters, likely key for mouse hetero-grooming behavior. Overall, a more comprehensive characterization of intricate molecular pathways linked to aberrant rodent grooming may markedly advance our understanding of underlying cellular mechanisms and related neurological disorders, eventually helping discover novel targets for their pharmacological or gene therapy interventions. [ABSTRACT FROM AUTHOR]

This cross-sectional study surveyed veterinarians and facility managers to characterise the use of antimicrobials in laboratory rodent facilities within Australia and New Zealand. Most facilities (71%) reported routine administration of antimicrobials. The indications for antibiotic use reflected those described in publications and differed significantly to reasons for use in non-laboratory animals. Antimicrobials used include those of critical importance to human health, and access to these drugs is unregulated, as prescription-only classes are ordered through research catalogues, without human or veterinary physician prescriptions. The ways in which antimicrobials are used in Australian and New Zealand rodent facilities are likely contributing to antimicrobial resistance within rodent populations, particularly as they are largely administered in drinking water, risking subtherapeutic dosing. Much antimicrobial use reported is unnecessary and could be replaced with changes to husbandry and handling. The generation of resistance in both pathogenic and commensal microbes may also represent a work health and safety issue for humans working with these animals. Reported disposal of antimicrobials included discharge into wastewater, without inactivation, and some respondents reported disposal of substrate, or soiled bedding, nesting material, and disposable enrichment items, from treated animals and medicated feed into landfill, without prior inactivation. Environmental contamination with resistant microbes and antimicrobials is a significant driver of antimicrobial resistance. As such, significant opportunities exist to implement judicious and responsible use of antimicrobials within research rodent facilities in Australia and New Zealand, with a particular focus on instituting aseptic surgery, optimising dosing regimens, and inactivation of medicated water and substrate before disposal. [ABSTRACT FROM AUTHOR]

Dysregulation of growth hormone (GH) signaling consistently leads to increased lifespan in laboratory rodents, yet the precise mechanisms driving this extension remain unclear. Understanding the molecular underpinnings of the beneficial effects associated with GH deficiency could unveil novel therapeutic targets for promoting healthy aging and longevity. In our pursuit of identifying metabolites implicated in aging, we conducted an unbiased lipidomic analysis of serum samples from growth hormone‐releasing hormone knockout (GHRH‐KO) female mice and their littermate controls. Employing a targeted lipidomic approach, we specifically investigated ceramide levels in GHRH‐KO mice, a well‐established model of enhanced longevity. While younger GHRH‐KO mice did not exhibit notable differences in serum lipids, older counterparts demonstrated significant reductions in over one‐third of the evaluated lipids. In employing the same analysis in liver tissue, GHRH‐KO mice showed pronounced downregulation of numerous ceramides and hexosylceramides, which have been shown to elicit many of the tissue defects that accompany aging (e.g., insulin resistance, oxidative stress, and cell death). Additionally, gene expression analysis in the liver tissue of adult GHRH‐KO mice identified substantial decreases in several ceramide synthesis genes, indicating that these alterations are, at least in part, attributed to GHRH‐KO‐induced transcriptional changes. These findings provide the first evidence of disrupted ceramide metabolism in a long‐lived mammal. This study sheds light on the intricate connections between GH deficiency, ceramide levels, and the molecular mechanisms influencing lifespan extension. [ABSTRACT FROM AUTHOR]

Human activities such as agriculturalization and domestication have led to the emergence of many new pathogens via host-switching events between humans, domesticated and wild animals. Staphylococcus aureus is a multi-host opportunistic pathogen with a global healthcare and economic burden. Recently, it was discovered that laboratory and wild rodents can be colonised and infected with S. aureus, but the origins and zoonotic potential of rodent S. aureus is unknown. In order to trace their evolutionary history, we employed a dataset of 1249 S. aureus genome sequences including 393 of isolates from rodents and other small mammals (including newly determined sequences for 305 isolates from 7 countries). Among laboratory mouse populations, we identified multiple widespread rodent-specific S. aureus clones that likely originated in humans. Phylogeographic analysis of the most common murine lineage CC88 suggests that it emerged in the 1980s in laboratory mouse facilities most likely in North America, from where it spread to institutions around the world, via the distribution of mice for research. In contrast, wild rodents (mice, voles, squirrels) were colonized with a unique complement of S. aureus lineages that are widely disseminated across Europe. In order to investigate the molecular basis for S. aureus adaptation to rodent hosts, genome-wide association analysis was carried out revealing a unique complement of bacteriophages associated with a rodent host ecology. Of note, we identified novel prophages and pathogenicity islands in rodent-derived S. aureus that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes promoting survival in new host-species. Author summary: New pathogens typically emerge after host-switching events, threatening public health and food security. Here we used an evolutionary genomic approach to reveal the origins of Staphylococcus aureus in laboratory and wild rodent populations. S. aureus in laboratory rodents appears to have originated in humans and following host jump events has spread around the world via the distribution of mice for research purposes. Distinct clones of S. aureus widely distributed around Europe are associated with wild rodent populations. We found unique types of prophages in rodent S. aureus that have played a central role in their emergence and expansion including some with genes encoding putative virulence factors. In particular, we identified novel prophages and pathogenicity islands that conferred the potential for coagulation of rodent plasma, a key phenotype of abscess formation and persistence. Taken together, our findings highlight the remarkable capacity of S. aureus to expand into new host populations, driven by the acquisition of genes acquired via mobile genetic elements. [ABSTRACT FROM AUTHOR]

Simple Summary: Light is vital to many aspects of normal physiological functioning and behavior; however, the ideal lighting conditions for laboratory rats is unknown. The aim of this study was to determine rats' preferences for the spectral make-up of light created by red or clear cages at high and low light levels (25 or 200 lux). Rats' preferences were tested three times with a free choice test as they matured. Most rats preferred dim light to bright light, no matter the color. But some rats from clear and bright cages preferred clear light more; however, this did change with experience. Furthermore, the rats' sex, type, and behavior mattered for their choices. This study concludes that darker environments are more likely to improve rat welfare by providing a condition they prefer, but the spectral make-up of the light created by red-tinted cages was not aversive. Light is a key factor influencing the welfare of laboratory rodents, but little is known about their optimal lighting condition. It i common knowledge that rats prefer dim light, so bright light is mitigated with red-tinted shelters or cages, which alter both the color and intensity of light. Because both aspects are altered, the contribution of each feature to rodent preference is unknown. Further, it is unknown if this preference is influenced by previous experience. We hypothesized that rats would prefer lower light intensity and that their preferences would be influenced by their housing environment. Breeder pairs of rats were randomly separated into four treatments groups: red 200 lux, red 25 lux, clear 200 lux, and clear 25 lux. The breeders' offspring were tested three times in an apparatus that offered access to each environment, and their preferences were analyzed. Generally, the rats preferred the lower-lux environments and showed no color preference. However, the rats from the clear, 200 lux cages, preferred clear caging and only showed a preference for 25 lux conditions during the second and third preference tests. These results suggest that the light intensity, more than color, should be considered when designing rodent housing and testing facilities. [ABSTRACT FROM AUTHOR]

Maternal behavior research in laboratory rats has revealed important behavioral and neurobiological mechanisms governing the onset, maintenance and decline of maternal behavior. However, the extent to which these mechanisms are evolutionarily conserved across species is less clear. This manuscript proposes that examining these mechanisms in dogs may be a viable approach to test their generality and help bridge the gap between rodent and human research, as domestic dogs show greater individual differences and exhibit more human-like maternal characteristics than rodents. These aspects represent advantages over rodent models, which in turn allow systems biological approaches not available in rodents. Additionally, domestic dogs share similar social environments with humans, suffer from the same mental disorders as humans, and can be treated with the same medications. This paper begins with a summary of key findings and theoretical developments from decades of rat maternal behavior research, followed by a literature review of the extant maternal behavior research on dogs and related methodology, highlighting the unique behavioral characteristics of dog maternal behavior and similarities and differences from rat maternal behavior. Finally, several knowledge gaps in dog maternal behavior research, as well as the future research in this area is discussed. It concludes that research on dog maternal behavior will not only advance our understanding of the universality of the neurobiological and behavioral mechanisms in maternal behavior, but also improve our understanding of risk factors associated with postpartum mental disorders. [ABSTRACT FROM AUTHOR]

Mounting evidence of the occurrence of direct and indirect interactions between the human blood fluke, Schistosoma mansoni, and the gut microbiota of rodent models raises questions on the potential role(s) of the latter in the pathophysiology of hepatointestinal schistosomiasis. However, substantial differences in both the composition and function between the gut microbiota of laboratory rodents and that of humans hinders an in-depth understanding of the significance of such interactions for human schistosomiasis. Taking advantage of the availability of a human microbiota-associated mouse model (HMA), we have previously highlighted differences in infection-associated changes in gut microbiota composition between HMA and wildtype (WT) mice. To further explore the dynamics of schistosome-microbiota relationships in HMA mice, in this study we (i) characterize qualitative and quantitative changes in gut microbiota composition of a distinct line of HMA mice (D2 HMA) infected with S. mansoni prior to and following the onset of parasite egg production; (ii) profile local and systemic immune responses against the parasite in HMA as well as WT mice and (iii) assess levels of faecal inflammatory markers and occult blood as indirect measures of gut tissue damage. We show that patent S. mansoni infection is associated with reduced bacterial alpha diversity in the gut of D2 HMA mice, alongside expansion of hydrogen sulphide-producing bacteria. Similar systemic humoral responses against S. mansoni in WT and D2 HMA mice, as well as levels of faecal lipocalin and markers of alternatively activated macrophages, suggest that these are independent of baseline gut microbiota composition. Qualitative comparative analyses between faecal microbial profiles of S. mansoni-infected WT and distinct lines of HMA mice reveal that, while infection-induced alterations of the gut microbiota composition are highly dependent on the baseline flora, bile acid composition and metabolism may represent key elements of schistosome-microbiota interactions through the gut-liver axis. [ABSTRACT FROM AUTHOR]

Animal welfare has evolved during the past decades to improve not only the quality of life of laboratory rodents but also the quality and reproducibility of scientific investigations. Bibliometric analysis has become an important tool to complete the current knowledge with academic databases. Our objective was to investigate whether scientific research on cannibalism/infanticide is connected with maternal aggression towards the offspring in laboratory rodents. To carry out our research, we performed a specific search for published articles on each concept. Results were analyzed in the open-source environment RStudio with the package Bibliometrix. We obtained 253 and 134 articles for the first search (cannibalism/infanticide) and the second search (maternal aggression towards the pups) respectively. We observed that the interest in infanticide/cannibalism started in the 1950s, while researchers started showing interest in maternal aggression towards the pups 30 years later. Our analyses indicated that maternal aggression had better citations in scientific literature. In addition, although our results showed some common features (e.g. oxytocin or medial preoptic area in the brain), we observed a gap between cannibalism/infanticide and maternal aggression towards the pups with only 14 published articles in common for both the searches. Therefore, we recommend researchers to combine both concepts in further investigations in the context of cannibalism for better dissemination and higher impact in laboratory rodents' welfare research. [ABSTRACT FROM AUTHOR]

Barbering is a behavior which involves the plucking or nibbling of fur, hair, or whiskers (vibrissae), leading to focal hair loss, and is often seen in laboratory mice and rats. The role of this behavior, including its relationship with stress, aggression, grooming, and aberrant stereotypic behavior, is actively discussed. Insights into the nature of barbering and its impact on laboratory rodents should be considered when planning experimental studies. Here, we discuss recent data on the neurobiology and genetics of barbering, as well as its role in the behavior and central nervous system of laboratory rodents. [ABSTRACT FROM AUTHOR]

Per- and polyfluoroalkyl substances (PFAS) are a large group of synthetic persistent chemicals, which are used in many industrial and commercial applications. Hundreds of different PFAS have been identified in the environment and they are commonly found also in human blood. Due to the chemical stability and extensive use, PFAS pose a risk for human health and wildlife. Mounting evidence indicates that PFAS-exposure adversely affects many organs including liver, kidney, and reproductive tissues and induces tumors in laboratory rodents. Epidemiological studies show association between PFAS-exposure and some tumors also in humans. Effects of PFAS-exposure are complex and obviously do not depend only on the concentration and the structure of PFAS, but also on age and sex of the exposed individuals. It has been difficult to show a causal link between PFAS-exposure and tumors. Moreover, molecular mechanisms of the PFAS effects in different tissues are poorly understood. PFAS are not directly mutagenic and they do not induce formation of DNA binding metabolites, and thus are assumed to act more through non-genotoxic mechanisms. In this review, we discuss the involvement of PFAS-compounds in tumor development in tissues where PFAS exposure has been associated with cancer in epidemiological and animal studies (liver, kidney, testicle and breast). We will focus on molecular pathways and mechanisms related to tumor formation following PFAS-exposure. [ABSTRACT FROM AUTHOR]

Concerns about poor animal to human translation have come increasingly to the fore, in particular with regards to cognitive improvements in rodent models, which have failed to translate to meaningful clinical benefit in humans. This problem has been widely acknowledged, most recently in the field of Alzheimer's disease, although this issue pervades the spectrum of central nervous system (CNS) disorders, including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Consequently, recent efforts have focused on improving preclinical to clinical translation by incorporating more clinically analogous outcome measures of cognition, such as touchscreen-based assays, which can be employed across species, and have great potential to minimize the translational gap. For aging-related research, it also is important to incorporate model systems that facilitate the study of the long prodromal phase in which cognitive decline begins to emerge and which is a major limitation of short-lived species, such as laboratory rodents. We posit that to improve translation of cognitive function and dysfunction, nonhuman primate models, which have conserved anatomical and functional organization of the primate brain, are necessary to move the field of translational research forward and to bridge the translational gaps. The present studies describe the establishment of a comprehensive battery of touchscreen-based tasks that capture a spectrum of domains sensitive to detecting aging-related cognitive decline, which will provide the greatest benefit through longitudinal evaluation throughout the prolonged lifespan of the marmoset. [ABSTRACT FROM AUTHOR]

The article discusses the efficacy of chlorine dioxide gas in destroying Syphacia muris eggs, which are commonly found in laboratory rodents. Chlorine dioxide gas is a powerful disinfectant that has antimicrobial activity against various microorganisms. The study found that chlorine dioxide gas at a concentration of 1mg per 4 hours or 4mg per 1 hour resulted in 100% kill of the eggs. This could be a useful tool in eradicating pinworms in animal facilities, as current disinfectants have limitations. The use of chlorine dioxide is considered safe and environmentally friendly. [Extracted from the article]

This review article delves into the details of the 3R-Refinement principles as a vital framework for ethically sound rodent research laboratory. It highlights the core objective of the refinement protocol, namely, to enhance the well-being of laboratory animals while simultaneously improving the scientific validity of research outcomes. Through an exploration of key components of the refinement principles, the article outlines how these ethics should be implemented at various stages of animal experiments. It emphasizes the significance of enriched housing environments that reduce stress and encourage natural behaviors, non-restraint methods in handling and training, refined dosing and sampling techniques that prioritize animal comfort, the critical role of optimal pain management and the importance of regular animal welfare assessment in maintaining the rodents well-being. Additionally, the advantages of collaboration with animal care and ethics committees are also mentioned. The other half of the article explains the extensive benefits of the 3R-Refinement protocol such as heightened animal welfare, enhanced research quality, reduced variability, and positive feedback from researchers and animal care staff. Furthermore, it addresses avenues for promoting the adoption of the protocol, such as disseminating best practices, conducting training programs, and engaging with regulatory bodies. Overall, this article highlights the significance of 3R-Refinement protocol in aligning scientific advancement with ethical considerations along with shaping a more compassionate and responsible future for animal research. [ABSTRACT FROM AUTHOR]

Neuroscience heavily relies on animal welfare in laboratory rodents as it can significantly affect brain development, cognitive function and memory formation. Unfortunately, laboratory animals are often raised in artificial environments devoid of physical and social stimuli, potentially leading to biased outcomes in behavioural assays. To assess this effect, we examined the impact of social and physical cage enrichment on various forms of motor coordination. Our findings indicate that while enriched-housed animals did not exhibit faster learning in eyeblink conditioning, the peak timing of their conditioned responses was slightly, but significantly, improved. Additionally, enriched-housed animals outperformed animals that were housed in standard conditions in the accelerating rotarod and ErasmusLadder test. In contrast, we found no significant effect of enrichment on the balance beam and grip strength test. Overall, our data suggest that an enriched environment can improve motor performance and motor learning under challenging and/or novel circumstances, possibly reflecting an altered state of anxiety. [ABSTRACT FROM AUTHOR]

Dystonia is a network disorder presumed to result from abnormalities in multiple brain regions and in multiple cell populations. The specific pathomechanisms affecting the motor circuits in dystonia are, however, still largely unclear. Animal models for dystonia have long been used to advance our understanding on how specific brain regions and cell populations are involved in dystonia symptomatogenesis. Lesioning, pharmacological modulation and electrical stimulation paradigms were able to highlight that both the basal ganglia and the cerebellum are pathologically altered in these animal models for dystonia. Techniques such as optogenetics and chemogenetics now offer the opportunity for targeted modulation of brain regions and most importantly cell populations and circuits. This could not only allow for a better understanding of the dystonic brain, but potentially improve and expand treatment options. In hopes that the insights from these neuromodulation techniques will eventually translate into therapies, we aimto summarize and critically discuss the findings fromdifferent in vivo approaches used to dissect the network dysfunctions underlying dystonia. [ABSTRACT FROM AUTHOR]

Creating of a scar model in laboratory animals is the most acceptable option for the preclinical search of scar treatment. However, due to high skin regeneration rate in laboratory rodents, creating an optimal animal model of scar formation is a challenge. Here we describe five methods for modeling a scar tissue in rats that we have tested. These methods allowed achieving different histopathological features and different stages of skin scar formation. [ABSTRACT FROM AUTHOR]

Laboratory studies with rodents indicate that in utero proximity of a female to male fetus can affect female's subsequent reproduction due to elevated testosterone exposure during early development. It remains unknown whether these findings can be generalised to non-laboratory species because the need for caesarean section makes it difficult to determine the intrauterine position outside laboratory conditions. As an alternative, some studies have compared the reproductive performance of individuals born in male-biased litters to those born in femalebiased litters. We identified 44 of those studies in 28 viviparous species for a total of 176 relationships between litter sex composition around the time of birth and subsequent reproductive performance (fertility, fecundity, age at first reproduction, interbirth intervals or post-natal survival of offspring). Those relationships are discordant and complex both within and across species. Some factors can mask an actual association between litter sex composition and reproductive performance. Conversely, a part of significant relationships between litter sex composition and reproductive performance likely arises via pathways other than androgen- and oestrogen-transfer between fetuses of different sexes. [ABSTRACT FROM AUTHOR]

Background: Heavy metals, such as lead harms animals' health. The objective of this study was to evaluate the level of Pb pollution in the cities of Golestan and Mazandaran Provinces by measuring Pb concentrations in the bloods of brown rats, which serve as omnivorous bioindicators living in the same habitat as humans. Methods: Eight highly populated cities were selected, with 10 rats trapped in each city. Blood samples were taken from the rats, and Pb measurements were done by atomic absorption spectrometry. Results: All sampled rats were Pb-contaminated. The mean Pb concentrations in different cities of Golestan Province were statistically similar (p > 0.05). In Mazandaran cities, however, significant differences in mean Pb concentrations were observed. The highest contamination was recorded in Neka (10.28 ± 0.97 µg/dL), while the lowest contamination was observed in Babol (7.3 ± 1.36 µg/dL). The mean Pb concentrations in the studied cities of Golestan (9.43 ± 1.81 µg/dL) and Mazandaran (9.02 ± 1.07 µg/dL) Provinces, as well as in male (10.38 µg/dL) and female (9.25 µg/dL) rats were similar. Conclusion: The Pb contaminations observed in the sampled rats are indicative of Pb contaminations of the sampled cities and the presence of Pb sources in these areas. It seems necessary to take precautionary procedures to prevent the entry of polluted effluents into the sampled cities and the consumption of Pb-contaminated gasoline in these areas, to prevent Pb contamination of human populations. [ABSTRACT FROM AUTHOR]

In the carotid body of laboratory rodents, adenosine 5′-triphosphate (ATP)-mediated transmission is regarded as critical for transmission from chemoreceptor type I cells to P2X3 purinoceptor-expressing sensory nerve endings. The present study investigated the distribution of P2X3-immunoreactive sensory nerve endings in the carotid body of the adult male Japanese monkey (Macaca fuscata) using multilabeling immunofluorescence. Immunoreactivity for P2X3 was detected in nerve endings associated with chemoreceptor type I cells immunoreactive for synaptophysin. Spherical or flattened terminal parts of P2X3-immunoreactive nerve endings were in close apposition to the perinuclear cytoplasm of synaptophysin-immunoreactive type I cells. Immunoreactivity for ectonucleoside triphosphate diphosphohydrolase 2 (NTPDase2), which hydrolyzes extracellular ATP, was localized in the cell body and cytoplasmic processes of S100B-immunoreactive cells. NTPDase2-immunoreactive cells surrounded P2X3-immunoreactive terminal parts and synaptophysin-immunoreactive type I cells, but did not intrude into attachment surfaces between terminal parts and type I cells. These results suggest ATP-mediated transmission between type I cells and sensory nerve endings in the carotid body of the Japanese monkey, as well as those of rodents. [ABSTRACT FROM AUTHOR]

Rats and mice are the most used experimental models in research. Globally, animal houses are subjected to parasite outbreaks. In Brazil, the parasitological profile is used to reflect the sanitary condition of laboratory animals and must be monitored frequently. The present study developed an integrative review of scientific studies on the parasitological profile of rats and mice in animal facilities in Brazil. It identified the most prevalent parasite species reported in animal facilities from different geographic regions of the country, as well as factors contributing to the perpetuation of these parasites, and proposed measures to help prevent such infections. Based on the guiding question “which endoparasites and ectoparasites have already been identified in rat and mouse colonies in animal facilities in Brazil?” and considering inclusion and exclusion criteria, 28 studies published between 1974 and 2021 were selected in four scientific bases. These studies covered facilities in 12 Brazilian States, describing 16 genera of parasites in mice and 18 in rats. Most of the facilities in the selected studies were of the conventional type and with few sanitary barriers, and these conditions may favor the recurrence of parasites. Efforts are, therefore,necessary for institutions to have animal facilities in accordance with the legislation and practice optimal methodologies. The measures proposed in this article can contribute to change the panorama of parasites in the national animal facilities, aiming to safeguard the quality of scientific data and animal welfare. [ABSTRACT FROM AUTHOR]

Suncus murinus is gaining prominence as a laboratory animal; however, there is no generally accepted method for microbiological monitoring. This study aimed to apply non-serological microbiological monitoring of laboratory mice for S. murinus and identify the subdominant species obtained by culture methods for microbial assessment. Culture and PCR were used to test S. murinus for the laboratory mice test panels including 10 bacterial species and orthohantaviruses, all of which were negative. The species that grew sub-dominantly in rectal feces were identified as Aeromonas hydrophila, which is pathogenic to mammals. These results indicate that microbiological monitoring should be used to detect pathogens directly from S. murinus, not from sentinel animals, due to the host-specific microbial environment. [ABSTRACT FROM AUTHOR]

Noise-induced tinnitus is generally associated with hearing impairment caused by traumatic acoustic overexposure. Previous studies in laboratory animals and human subjects, however, have observed differences in tinnitus susceptibility, even among individuals with similar hearing loss. The mechanisms underlying increased sensitivity or, conversely, resistance to tinnitus are still incompletely understood. Here, we used behavioral tests and ABR audiometry to compare the sound-evoked responses of mice that differed in the presence of noise-induced tinnitus. The aim was to find a specific pre-exposure neurophysiological marker that would predict the development of tinnitus after acoustic trauma. Noiseexposed mice were screened for tinnitus-like behavior with the GPIAS paradigm and subsequently divided into tinnitus (+T) and non-tinnitus (−T) groups. Both groups showed hearing loss after exposure, manifested by elevated audiometric thresholds along with reduced amplitudes and prolonged latencies of ABR waves. Prior to exposure, except for a slightly increased slope of growth function for ABR amplitudes in +T mice, the two groups did not show significant audiometric differences. Behavioral measures, such as the magnitude of the acoustic startle response and its inhibition by gap pre-pulse, were also similar before exposure in both groups. However, +T mice showed significantly increased suppression of the acoustic startle response in the presence of background noise of moderate intensity. Thus, increased modulation of startle by background sounds may represent a behavioral correlate of susceptibility to noise-induced tinnitus, and its measurement may form the basis of a simple non-invasive method for predicting tinnitus development in laboratory rodents. [ABSTRACT FROM AUTHOR]

The biological effects of densely-ionizing radiations such as neutrons and heavy ions encountered in space travel, nuclear incidents, and cancer radiotherapy, significantly differ from those of sparsely-ionizing photons and necessitate a comprehensive understanding for improved protection measures. Data on lifespan studies of laboratory rodents exposed to fission neutrons, accumulated in the Janus archive, afford unique insights into the impact of densely ionizing radiation on mortality from cancers and various organ dysfunction. We extracted and analyzed data for 21,308 individual B6CF1 mice to investigate the effects of neutron dose, fractionation, protraction, age, and sex on mortality. As Cox regression encountered limitations owing to assumption violations, we turned to Random Survival Forests (RSF), a machine learning algorithm adept at modeling nonlinear relationships. RSF interpretation using Shapley Additive Explanations revealed a dose response for mortality risk that curved upwards at low doses < 20 cGy, became nearly-linear over 20–150 cGy, and saturated at high doses. The response was enhanced by fractionation/protraction of irradiation (exhibiting an inverse dose rate effect), and diminished by older age at exposure. Somewhat reduced mortality was predicted for males vs females. This research expands our knowledge on the long-term effects of densely ionizing radiations on mammal mortality. [ABSTRACT FROM AUTHOR]

Considerable research has focused on how gonadal steroids, especially testosterone, modulate central nervous system control of aggression. Here, we outline a novel, extra-gonadal mechanism underlying the androgenic regulation of aggression. The seasonal switch hypothesis postulates that the pineal hormone melatonin acts on the adrenal glands, and possibly the brain, to modulate androgen release and its subsequent conversion to regulate aggressive behavior. This model extends our understanding of the neural and neuroendocrine mechanisms controlling aggressive behavior and violence across vertebrate species and environmental contexts. Aggression is a well-studied social behavior that is universally exhibited by animals across a wide range of contexts. Prevailing knowledge suggests gonadal steroids primarily mediate aggression; however, this is based mainly on studies of male–male aggression in laboratory rodents. When males and females of other species, including humans, are examined, a positive relationship between gonadal steroids and aggression is less substantiated. For instance, hamsters housed in short 'winter-like' days show increased aggression compared with long-day housed hamsters, despite relatively low circulating gonadal steroids. These results suggest alternative, non-gonadal mechanisms controlling aggression. Here, we propose the seasonal switch hypothesis, which employs a multidisciplinary approach to describe how seasonal variation in extra-gonadal steroids, orchestrated by melatonin, drives context-specific changes in aggression. [ABSTRACT FROM AUTHOR]

Smooth muscle tissue (SMT) is one of the main structural components of visceral organs, acting as a key factor in the development of adaptive and pathological conditions. Despite the crucial part of SMT in the gastrointestinal tract activity, the mechanisms of its gravisensitivity are still insufficiently studied. The study evaluated the content of smooth muscle actin (α-SMA) in the membranes of the gastric fundus and jejunum in C57BL/6N mice (30-day space flight), in Mongolian gerbils Meriones unguiculatus (12-day orbital flight) and after anti-orthostatic suspension according to E.R. Morey-Holton. A morphometric analysis of α-SMA in the muscularis externa of the stomach and jejunum of mice and Mongolian gerbils from space flight groups revealed a decreased area of the immunopositive regions, a fact indicating a weakening of the SMT functional activity. Gravisensitivity of the contractile structures of the digestive system may be due to changes in the myofilament structural components of the smooth myocytes or myofibroblast actin. A simulated antiorthostatic suspension revealed no significant changes in the content of the α-SMA expression level, a fact supporting an alteration in the functional properties of the muscularis externa of the digestive hollow organs under weightless environment. The data obtained contribute to the novel mechanisms of the SMT contractile apparatus remodeling during orbital flights and can be used to improve preventive measures in space biomedicine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Food grinding is a behavior that occurs in rodents, supposedly affected by a variety of circumstances. It is yet unclear how these elements affect food grinding. The purpose of this study was to investigate the relationship between the gut microbiota and food grinding, as well as the impact of varying food supplies on this behavior. Our research showed that food restriction may change the abundance of the gut microbiota and its metabolites as well as reduce the amount of ground food to a larger extent than its effect on food consumption. Therefore, the inhibition of food grinding in Brandt's voles may be attributed in part to differences in the abundance of gut microbiome and their metabolite, short-chain fatty acids, which is induced by food restriction. This study suggests that reducing the food supply could effectively inhibit food grinding during laboratory rodent feeding. Food grinding is supposed to be influenced by multiple factors. However, how those factors affecting this behavior remain unclear. In this study, we investigated the effect of food restriction on food grinding in Brandt's voles (Lasiopodomys brandtii), as well as the potential role of the gut microbiota in this process, through a comparison of the variations between voles with different food supplies. Food restriction reduced the relative amount of ground food to a greater extent than it lowered the relative food consumption, and altered the abundance of Staphylococcus, Aerococcus, Jeotgalicoccus, and Un--s-Clostridiaceae bacterium GM1. Fecal acetate content for the 7.5 g-food supply group was lower than that for the 15 g-food supply group. Our study indicated that food restriction could effectively inhibit food grinding. Further, Un--s-Clostridiaceae bacterium GM1 abundance, Aerococcus abundance, and acetate content were strongly related to food grinding. Variations in gut microbial abundance and short-chain fatty acid content induced by food restriction likely promote the inhibition of food grinding. These results could potentially provide guidance for reducing food waste during laboratory rodent maintenance. [ABSTRACT FROM AUTHOR]

Gestational protein intake restriction-induced long-lasting harmful outcomes in the offspring's organs and systems. However, few studies have focused on this event's impact on the brain's structures and neurochemical compounds. The present study investigated the effects on the amygdala neurochemical composition and neuronal structure in gestational protein-restricted male rats' offspring. Dams were maintained on isocaloric standard rodent laboratory chow with regular protein [NP, 17%] or low protein content [LP, 6%]. Total cells were quantified using the Isotropic fractionator method, Neuronal 3D reconstruction, and dendritic tree analysis using the Golgi–Cox technique. Western blot and high-performance liquid chromatography performed neurochemical studies. The gestational low-protein feeding offspring showed a significant decrease in birth weight up to day 14, associated with unaltered brain weight in youth or adult progenies. The amygdala cell numbers were unchanged, and the dendrites length and dendritic ramifications 3D analysis in LP compared to age-matched NP progeny. However, the current study shows reduced amygdala content of norepinephrine, epinephrine, and dopamine in LP progeny. These offspring observed a significant reduction in the amygdala glucocorticoid (GR) and mineralocorticoid (MR) receptor protein levels. Also corticotrophin-releasing factor (CRF) amygdala protein content was reduced in 7 and 14-day-old LP rats. The observed amygdala neurochemical changes may represent adaptation during embryonic development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition stress can alter the amygdala's neurochemical content and may contribute to known behavioral changes induced by gestational protein restriction. [ABSTRACT FROM AUTHOR]

In today's post-genomic era, it is crucial to rethink the concept of model organisms. While a few historically well-established organisms, e.g. laboratory rodents, have enabled significant scientific breakthroughs, there is now a pressing need for broader inclusion. Indeed, new organisms and models, from complex microbial communities to holobionts, are essential to fully grasp the complexity of biological principles across the breadth of biodiversity. By fostering collaboration between biology, advanced molecular science and omics communities, we can collectively adopt new models, unraveling their molecular functioning, and uncovering fundamental mechanisms. This concerted effort will undoubtedly enhance human health, environmental quality, and biodiversity conservation. The concept of model organisms in biological studies needs to be re-evaluated to reflect novel technological advances and help further scientific discovery. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to evaluate the pain associated with six methods of euthanasia: pentobarbital, CO2, decapitation, isoflurane, ketamine + xylazine, and ketamine + CO2 in Wistar rats, by applying the Rat Grimace Scale (RGS), comparing the scores, and determining the method with the highest score that might indicate pain in laboratory rodents. According to the results, during the application of the euthanasia method, the intraperitoneal administration of ketamine + xylazine and decapitation caused the highest RGS scores (0.6 ± 0.26 and 0.6 ± 0.16, respectively) (p < 0.0001), while after the application of the euthanasia methods, CO2 and isoflurane recorded the highest scores (p < 0.0001) (0.9 ± 0.18 and 1.2 ± 0.20, respectively). The results might indicate that injection and guillotine use could cause short-term pain in rodents, while high isoflurane scores could be associated with nociception/pain or the myorelaxant properties of the drug. Further research is needed to establish a comprehensive study of pain during euthanasia, where the RGS could be used minding the limitations that anesthetics might have on facial expression. Refinement of experimental procedures in animal research has the objective of preventing and minimizing pain/distress in animals, including the euthanasia period. This study aimed to evaluate pain associated with six methods of euthanasia in Wistar rats (injectable, inhalational, and physical), by applying the Rat Grimace Scale (RGS), comparing the scores, and determining the method with the highest score that might indicate pain for laboratory rodents. Sixty adult male and female Wistar rats were used and assigned to six treatments: pentobarbital, CO2, decapitation, isoflurane, ketamine + xylazine, and ketamine + CO2. Video recording to assess the RGS scores was performed in four events: basal: 24 h before the procedure; Ti1: three minutes before the procedure; Ti2: during the application of the euthanasia method; and Ti3: immediately after the application until LORR. The main findings of this study showed that, during Ti2, decapitation and ketamine + xylazine had the highest scores (0.6 ± 0.26 and 0.6 ± 0.16, respectively) (p < 0.0001), while at Ti3, CO2 (0.9 ± 0.18) and isoflurane (1.2 ± 0.20) recorded the highest scores (p < 0.0001). According to the present results, decapitation and ketamine + xylazine elicited short-term acute pain, possibly due to tissue damage caused by both methods (injection and guillotine). In contrast, isoflurane's RGS scores recorded during Ti3 might be associated with nociception/pain due to the pungency of the drug or to the pharmacological muscle relaxant effect of isoflurane. Further research is needed to establish a comprehensive study of pain during euthanasia, where RGS could be used minding the limitations that anesthetics might have on facial expression. [ABSTRACT FROM AUTHOR]

Alpha-amylase is the main enzyme for starch digestion in the mammalian gastrointestinal tract. There are species differences in the enzymatic activity of pancreatic amylase that are related to the digestive strategy and natural diet of a species. This aspect is well investigated in pet and farm animals, while in common laboratory animal rodents, information is scarce. In the context of the 3R concept, detailed knowledge of the digestive physiology should be the basis of adequate nutrition, experimental planning and data interpretation. The present study aimed to obtain reference data on amylase activity in pancreatic tissue and duodenal digesta in laboratory mice, rats and hamsters. In addition, digesta was stained with Lugol's iodine to visualize starch in the process of degradation throughout the gastrointestinal tract. Amylase activity in pancreatic tissue and duodenal digesta was significantly lower in hamsters than rats and mice. The Lugol staining showed intense starch degradation in the hamsters' forestomachs, presumably by microbial fermentation. A possible explanation is that the prae-duodenal microbial starch fermentation enhances digestibility and reduces the need for pancreatic amylase in hamsters. Rats and mice may rely more on pancreatic amylase for prae-caecal starch digestion, while the microbial fermentation is mainly located in the caecum. The results clearly show species differences in the digestive capacity for starch in mice, rats and hamsters that need to be considered in the feeding of these species in the laboratory setting as well as in the use of rodents as translational animal models. [ABSTRACT FROM AUTHOR]

The Animal Metabolite Database (AMDB, https://amdb.online) is a freely accessible database with built-in statistical analysis tools, allowing one to browse and compare quantitative metabolomics data and raw NMR and MS data, as well as sample metadata, with a focus on the metabolite concentrations rather than on the raw data itself. AMDB also functions as a platform for the metabolomics community, providing convenient deposition and exchange of quantitative metabolomic data. To date, the majority of the data in AMDB relate to the metabolite content of the eye lens and blood of vertebrates, primarily wild species from Siberia, Russia and laboratory rodents. However, data on other tissues (muscle, heart, liver, brain, and more) are also present, and the list of species and tissues is constantly growing. Typically, every sample in AMDB contains concentrations of 60–90 of the most abundant metabolites, provided in nanomoles per gram of wet tissue weight (nmol/g). We believe that AMDB will become a widely used tool in the community, as typical metabolite baseline concentrations in tissues of animal models will aid in a wide variety of fundamental and applied scientific fields, including, but not limited to, animal modeling of human diseases, assessment of medical formulations, and evolutionary and environmental studies. [ABSTRACT FROM AUTHOR]

The development of robots as tools for biological research, sometimes termed “biorobotics”, has grown rapidly in recent years, fueled by the proliferation of miniaturized computation and advanced manufacturing techniques. Much of this work is focused on the use of robots as biomechanical models for natural systems. But, increasingly, biomimetic robots are being employed to interact directly with animals, as component parts of ethology studies in the field and behavioral neuroscience studies in the laboratory. While it has been possible to mechanize and automate animal behavior experiments for decades, only recently has there been the prospect of creating at-scale robotic animals containing the sensing, autonomy and actuation necessary for complex, life-like interaction. This not only opens up new avenues of enquiry, but also provides important ways to improve animal welfare, both by reducing or replacing the use of animal subjects, and by minimizing animal distress (if robots are used judiciously). This article will discuss the current state of the art in robotic lab rats, providing perspective on where research could be directed to enable the safe and effective use of biorobotic animals.

It is commonly accepted now that a number of neuropsychiatric diseases are associated with early life stress. Various rodent models are used to elucidate the pathogenetic mechanisms of psychopathologies that cannot be studied in humans. Adequate data translation requires a comparison of neuroontogenetic processes at the moment of exposure and in further ontogenesis. There is a plenty of comparative studies on the development of neurons and neuronal networks, as well as changes in the hypothalamic–pituitary–adrenal axis. Recently, it has been shown that glial cells are actively entrained both in brain development and in its response to stress. The opinion that it is microglia and astrocytes that represent most promising targets for therapeutic intervention in stress-related diseases is gaining further supported. However, there are still no comparative studies encompassing both stress implementation systems per se, as well as neuronal and glial developmental markers. In an attempt to fill the gap, this review may provide the view from a new angle on the challenges of childhood stress modeling and data translation. The review is organized as a comparative analysis of the parallel key neuroontogenetic events in laboratory rodents and humans during the stress-hyporesponsive period, which may ensure a more accurate matching between the different stages of brain development in laboratory rodents and humans. The data presented here may also help outline some growth points and raise new issues associated with stress in early ontogeny. [ABSTRACT FROM AUTHOR]

Background: The Rotarod test with commercial apparatus is widely used to assess locomotor performance, balance and motor learning as well as the deficits resulting from diverse neurological disorders in laboratory rodents due to its simplicity and objectivity. Traditionally, the test ends when rodents drop from the accelerating, turning rod, and the only parameter used commonly is "latency to fall". The values of individual animals can often vary greatly. Results: In the present study, we established a procedure for mice with 4 consecutive days of training with 4 trials per day and modified the testing procedure by placing the mice back on the rod repeatedly after each fall until the trial ends (5 min). Data from the fourth training day as baseline results showed that the second, third and fourth trial were more consistent than the first, probably due to habituation or learning. There was no difference between the second, third and fourth trial, two trials may be sufficient in testing. We also introduced 3 additional read-outs: Longest duration on the rod (s), Maximal distance covered (cm), and Number of falls to better evaluate the motor capacity over the 5 min of testing. We then used this 4-parameter analysis to capture the motor deficits of mice with mild to moderate traumatic brain injuries (by a weight dropping on the skull (Marmarou model)). We found that normalization of data to individual baseline performance was needed to reduce individual differences, and 4 trials were more sensitive than two to show motor deficits. The parameter of Maximal distance was the best in detecting statistically significant long-term motor deficits. Conclusions: These results show that by making adjustments to the protocol and employing a more refined analysis, it is possible to expand a widely used routine behavioral test with additional accessible parameters that detect relevant deficits in a model of mild to moderate traumatic brain injury. The modified Rotarod test maybe a valuable tool for better preclinical evaluations of drugs and therapies. [ABSTRACT FROM AUTHOR]

Imaging technologies can help reduce the number of research animals used in scientific experiments. The 3Rs principle, which promotes ethical animal research, includes reduction as one of its principles. By using imaging techniques, scientists can study the organs and functions of live animals without harming or killing them. This allows for long-term studies and reduces the overall number of animals needed for research. Imaging technologies such as CT scans, MRI, nuclear imaging, optical imaging, and ultrasound are used to visualize the structure and function of internal organs in animals. This not only improves the quality of research studies but also helps scientists detect signs of discomfort and improve animal welfare. Overall, imaging technologies contribute to the reduction of research animals and support the 3Rs principle. [Extracted from the article]

Activation of brown adipose tissue (BAT) thermogenesis impacts energy balance and must be tightly regulated. Several neurotrophic factors, expressed in BAT of adult laboratory rodents, have been implicated in remodeling the sympathetic neural network to enhance thermogenesis [e.g., nerve growth factor (NGF), neuregulin-4 (NRG4), and S100b]. Here, we compare, to our knowledge, for the first time, the relative roles of three neurotrophic "batokines" in establishing/remodeling innervation during postnatal development and adult cold stress. We used laboratory-reared Peromyscus maniculatus, which rely heavily on BAT-based thermogenesis for survival in the wild, beginning between postnatal days (P) 8 and 10. BAT sympathetic innervation was enhanced from P6 to P10, and exogenous NGF, NRG4, and S100b stimulated neurite outgrowth from P6 sympathetic neurons. Endogenous BAT protein stores and/or gene expression of NRG4, S100b, and calsyntenin-3β (which may regulate S100b secretion) remained high and constant during development. However, endogenous NGF was low and ngf mRNA was undetectable. Conditioned media (CM) from cultured P10 BAT slices stimulated neurite outgrowth from sympathetic neurons in vitro, which was inhibited by antibodies against all three growth factors. P10 CM had significant amounts of secreted NRG4 and S100b protein, but not NGF. By contrast, BAT slices from cold-acclimated adults released significant amounts of all three factors relative to thermoneutral controls. These data suggest that although neurotrophic batokines regulate sympathetic innervation in vivo, their relative contributions differ depending on the life stage. They also provide novel insights into the regulation of BAT remodeling and BAT's secretory role, both of which are critical to our understanding of mammalian energy homeostasis. [ABSTRACT FROM AUTHOR]

Onchocerciasis, the second leading infectious cause of blindness, afflicts approximately 21 million people globally. Its control is limited to the use of the microfilaricidal drugs, ivermectin and moxidectin. Both drugs are unable to kill the adult worms which can survive for up to 15 years in patients, justifying the urgent need for potent and novel macrofilaricides that kill adult worms. The development of such drugs has been hindered by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo. This study assessed the survival of O. ochengi female worms and their embryos over time in two laboratory rodents: gerbils and hamsters and tested using "proof-of-concept" studies, whether known macrofilaricidal drugs can kill these worms. Animals were surgically implanted with mechanical or collagenase-liberated O. ochengi worm masses, and necropsied at various time points to test for survival. Recovered worm masses were assessed for viability by biochemical analysis (MTT/formazan assay) or fecundity (embryogram). Flubendazole (FBZ) administered at 20 mg/kg body weight was used to validate both rodent models. By day 26 post-implantation of 15 worm masses, a median of 7.00 (4.00–10.00) was recovered from hamsters, and 2.50 (2.00–4.00) from gerbils. Worm masses recovered from gerbils were mostly disintegrated or fragmented, with significantly higher fragmentation observed with collagenase-liberated worm masses. FBZ had no significant effect on the number of worm masses recovered, but enhanced embryo degradation in gerbils and reduced worm mass viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. ochengi. The hamsters appeared to maintain the worms longer, compared to gerbils. [ABSTRACT FROM AUTHOR]

Vision is the most essential sense system for the human being. Congenital visual impairment affects millions of people globally. It is increasingly realized that visual system development is an impressionable target of environmental chemicals. However, due to inaccessibility and ethical issues, the use of humans and other placental mammals is constrained, which limits our better understanding of environmental factors on ocular development and visual function in the embryonic stage. Therefore, as complementing laboratory rodents, zebrafish has been the most frequently employed to understand the effects of environmental chemicals on eye development and visual function. One of the major reasons for the increasing use of zebrafish is their polychromatic vision. Zebrafish retinas are morphologically and functionally analogous to those of mammalian, as well as evolutionary conservation among vertebrate eye. This review provides an update on harmful effects from exposure to environmental chemicals, involving metallic elements (ions), metal-derived nanoparticles, microplastics, nanoplastics, persistent organic pollutants, pesticides, and pharmaceutical pollutants on the eye development and visual function in zebrafish embryos. The collected data provide a comprehensive understanding of environmental factors on ocular development and visual function. This report highlights that zebrafish is promising as a model to identify hazardous toxicants toward eye development and is hopeful for developing preventative or postnatal therapies for human congenital visual impairment. [ABSTRACT FROM AUTHOR]