Implementing the 3Rs in Laboratory Animal Research - From Theory to Practice

Editorial of the Special Issue "Implementing the 3Rs in Laboratory Animal Research—From Theory to Practice

Isolamendu soziala, estres kronikoa eta depresioa

Ingurumen-estimulu batek aldaketak eragin ditzake garuneko neurokimikan eta nahasmendu neuropsikiatrikoak eragin. Hori horrela, isolamendu sozialak eragindako bakardade-sentimenduek eragina izan dezakete estres kronikoan. Estres kronikoak aldaketa neuroendokrinoak eta immunologikoak eragiten ditu, eta aldaketa horiek serotonina maila gutxitzea eragin lezakete garunean eta, ondorioz, depresioa eragin. Artikulu honetan, gizarte-isolamenduak eragindako depresioaren neurobiologian egin diren aurrerapenak deskribatzen dira.; An environmental stimulus can cause changes in brain neurochemistry, causing neuropsychiatric disorders. Feelings of loneliness caused by social isolation can lead to chronic stress and neuroendocrine and immunological changes. These changes could lead to a decrease in serotonin, which is common in people with depression. This article describes the advances in the neurobiology of the depression caused by social isolation

Mice in translational neuroscience: What R we doing?

Animal models play a pivotal role in translational neuroscience but recurrent problems in data collection, an-alyses, and interpretation, lack of biomarkers, and a tendency to over-reliance on mice have marred neuroscience progress, leading to one of the highest attrition rates in drug translation. Global initiatives to improve repro-ducibility and model selection are being implemented. Notwithstanding, mice are still the preferred animal species to model human brain disorders even when the translation has been shown to be limited. Non-human primates are better positioned to provide relevant translational information because of their higher brain complexity and homology to humans. Among others, lack of resources and formal training, strict legislation, and ethical issues may impede broad access to large animals. We propose that instead of increasingly restrictive legislation, more resources for training, education, husbandry, and data sharing are urgently needed. The cre-ation of multidisciplinary teams, in which veterinarians need to play a key role, would be critical to improve translational efficiency. Furthermore, it is not usually acknowledged by researchers and regulators the value of comparative studies in lower species, that are instrumental in toxicology, target identification, and mechanistic studies. Overall, we highlight here the need for a conceptual shift in neuroscience research and policies to reach the patients

Postweaning Grouping as a Strategy to Reduce Singly Housed Male Mice

Rearing laboratory mice in groups is important since social isolation after weaning induces brain alterations, which entails behavioral abnormalities in adulthood. Age is an important factor when grouping males of different litters due to inter-male aggressiveness. The aim of this study was to determine whether newly weaned mice could safely be grouped with late juvenile or early and late pubescent mice, and whether cage cleaning, the number of the hosting group members and testosterone plasma levels have any influence. Newly weaned C57BL/6J, CD1, and SCID Beige male mice were systematically grouped with same strain late juvenile, early or late pubescent male mice in clean or dirty cages of 1, 2 or 3 hosting members. We also analyzed plasma testosterone levels at different postnatal days. Our result showed that only strain and hosting male’s age influence agonistic behavior toward newly weaned mice. Thus, in order not to house a recently weaned male alone, we would recommend grouping it with late juvenile same strain mice in all studied strains. In the same way, CD1 and SCID Beige pubescent mice will admit a newly weaned mouse in their group. However, we would not recommend grouping newly weaned and pubescent C57BL/6J males

A survey on the use of mice, pigs, dogs and monkeys as animal models in biomedical research in Spain

[EN] Background The use of animals in biomedical science remains controversial. An individual's level of concern is generally influenced by their culture, previous or current experience with animals, and the specific animal species in question. In this study we aimed to explore what people in Spain who had never or who no longer worked with laboratory animals thought of the use of mice, pigs, dogs and monkeys for biomedical research purposes. We also aimed to determine whether or not people currently involved in biomedical research with the aforementioned species felt their work was justified. Results The study comprised a total of 807 participants (never worked = 285, used to work = 56, currently working = 466), almost two thirds of whom were women. Our results revealed that the phylogenetic scale is an important factor in people's opinions of the use of certain species in research. The percentage of people who were against the use of dogs or monkeys was higher than that of those who were against the use of mice or pigs. The main reasons given for having stopped working with laboratory animals were change of professional career and change in research project. Participants who were currently working with animals believed that their work was justified, but said they did not talk about it with people outside their immediate social circle. Conclusions Our findings suggest that there is a difference in moral status between monkeys and mice, as well as between companion animals (dogs) and farm animals (pigs). Our results support the idea that working with laboratory animals is a sensitive issue in Spain.The research of G.A. is supported by Grants from University of Basque Country (UPV/EHU)-Psicobiologia PPGI19/14

Working with laboratory rodents in Spain: a survey on welfare and wellbeing

[EN] Background: Replacement, reduction and refinement, the 3R principles, provide a framework to minimize the use and suffering of animals in science. In this context, we aimed to determine the actual perception that individuals working with laboratory rodents in biomedical research have on animal welfare and on their interaction with the animals, as well as how they perceive its impact on their social relations. To this end, we designed an anonymous on-line survey for people working with rodents, at three responsibility levels, in Spain. Results: Of the 356 participants, 239 were women (67 %); 263 were researchers (74%), and 93 animal facility staff (26%), of which 55 were caretakers/technicians (15 %), and 38 welfare officer/veterinarians (11 %). Animal facility staff indicated environmental enrichment to be a universal practice. About half of the participants reported that, in their opinion, animals suffer “little to none” or “minor” stress and pain. Animal caretakers/technicians and researchers perceived higher levels of stress and pain than welfare officers/veterinarians. Participants judged decapitation the most unpleasant method to kill rodents, whereas anaesthetic overdose was the least one. A sizable proportion − 21% of animal caretakers/technicians and 11.4% of researchers - stated that they were never given the choice not to euthanize the rodents they work with. Overall, women reported higher interactions with animals than men. Nevertheless, we could detect a significant correlation between time spent with the animals and interaction scores. Notably, 80% of animal facility staff and 92% of researchers rarely talked about their work with laboratory rodents with people outside their inner social circle. Conclusions: Overall, the participants showed high awareness and sensitivity to rodent wellbeing; animal facility staff reported a similar perception on welfare questions, independently of their category, while researchers, who spent less time with the animals, showed less awareness and manifested lower human-animal interaction and less social support. Regarding the perception on social acceptance of laboratory animal work, all groups were cautious and rarely talked about their job, suggesting that it is considered a sensitive issue in Spain.The research of G.A. is supported by grants from University of Basque Country (UPV/EHU) - Psicobiologia PPGI19/14 and GIU18/103

Looking Backward to Move Forward: a Meta-Analysis of Stem Cell Therapy in Amyotrophic Lateral Sclerosis

Transplantation of several types of stem cells (SC) for the treatment of amyotrophic lateral sclerosis (ALS) has been evaluated in numerous Phase I/II clinical trials with inconclusive results. Here, we conducted a meta-analysis to systematically assess the outcome of SC therapy trials which report the evolution of each patient before and after cell administration. In this way, we aimed to determine the effect of the SC intervention despite individual heterogeneity in disease progression. We identified 670 references by electronic search and 90 full-text studies were evaluated according to the eligibility criteria. Eleven studies were included comprising 220 cell-treated patients who received mesenchymal (M) SC (n=152), neural (N) SC (n=57), or mononuclear cells (MNC: CD34, CD117, and CD133 positive cells) (n=11). Our analyses indicate that whereas intrathecal injection of mesenchymal stromal cells appears to have a transient positive effect on clinical progression, as measured by the ALS functional rating score, there was a worsening of respiratory function measured by forced vital capacity after all interventions. Based on current evidence, we conclude that optimal cell product and route of administration need to be determined in properly controlled preclinical models before further advancing into ALS patients. In addition, in-depth understanding of disease mechanisms in subsets of patients will help tailoring SC therapy to specific targets and increase the likelihood of improving outcomesR.S.P. is the recipient of a Talentia Senior grant from the Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades of the Andalusian Government. L.M. is partly supported by the AGING Project for Department of Excellence at the Department of Translational Medicine (DIMET), Università del Piemonte Orientale, Novara, Italy

Fundamentos de neurociencia conductual

142 p.Los apuntes que se presentan a continuación pretenden ofrecer al estudiante una guía para abordar la asignatura de Fundamentos de Neurociencia Conductual. Esta asignatura tiene como objetivo conocer las bases neurofisiológicas que subyacen a la conducta. Es, así, una materia básica para poder abordar el estudio del resto de las asignaturas que configuran el bloque o módulo formativo “Bases Biológicas de la Conducta” en la Facultad de Psicología de la Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU). Este módulo pretende que los estudiantes comprendan la relación comportamiento-sistema nervioso a través de las aportaciones que la neurociencia ofrece a la comprensión de la conducta humana, para poder así integrar esta perspectiva en la explicación del comportamiento y de los procesos mentales

Professional Quality of Life in Research Involving Laboratory Animals

Many workers contribute to the success of animal welfare and study outcomes in biomedical research. However, the professional quality of life (ProQoL) of those who work with laboratory animals has not been explored in Spain. To this end, we adapted the ProQoL scale to the Spanish population working with laboratory animals. Participants were contacted by email and asked to complete an anonymous on-line questionnaire. The study comprised a total of 498 participants, 12.4% welfare officers/veterinarians, 19.5% caretaker/technicians, 13.9% principal investigators, 20.7% investigators, 13.6% research technicians, and 19.9% PhD students. The adapted scale revealed very good reliability and internal validity, providing information about two different subscales, compassion satisfaction and compassion fatigue. Animal-facility personnel showed higher total ProQoL and compassion-satisfaction scores than researchers; PhD students showed the lowest scores. Thus, our results indicate that job category is a contributing factor in perceived professional quality of life. We observed that compassion satisfaction is negatively associated with the perceived animal stress/pain. Participants reporting poorer compassion satisfaction also reported lower social-support scores. Overall, our ProQoL scale is a useful tool for analyzing the professional quality of life in the Spanish population, and may help to design future interventions to improve workplace wellbeing in Spain and other Spanish-speaking populations.The research of G.A. is supported by grants from the University of Basque Country (UPV/EHU)—Psicobiologia PPGI19/14 and GIU18/103

Individualized Housing Modifies the Immune–Endocrine System in CD1 Adult Male Mice

In the last years, different research groups have made considerable efforts to improve the care and use of animals in research. Mice (Mus musculus) are the most widely used animal species in research in the European Union and are sociable and hierarchical creatures. During experiments, researchers tend to individualize males, but no consideration is given to whether this social isolation causes them stress. The aim of this study was, therefore, to explore whether 4 weeks of social isolation could induce changes in different physiological parameters in adult Crl:CD1(ICR) (CD1) males, which may interfere with experimental results. Body weight, blood cells, and fecal corticosterone metabolites levels were the analyzed parameters. Blood and fecal samples were collected at weeks 1 and 4 of the experimental procedure. Four weeks of single housing produced a significant time-dependent decrease in monocytes and granulocytes. Fecal corticosterone metabolite levels were higher in single-housed mice after 1 week and then normalized after 4 weeks of isolation. Body weight, red blood cells, and platelets remained unchanged in both groups during this period. We can, therefore, conclude that social isolation affects some immune and endocrine parameters, and that this should be taken into account in the interpretation of research data.This study was supported by the University of the Basque Country (UPV/EHU) GIU18/103 grant