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

ABSTRACT: 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.

SUBMITTER: Ortega-Saez I

PROVIDER: S-EPMC10044133 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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

Ortega-Saez Iván I Díez-Solinska Alina A Grífols Roger R Martí Cristina C Zamora Carolina C Muñoz-Culla Maider M Vegas Oscar O Azkona Garikoitz G

Animals : an open access journal from MDPI 20230310 6

In the last years, different research groups have made considerable efforts to improve the care and use of animals in research. Mice (<i>Mus musculus</i>) 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 isolati ...[more]

PMID: 36978567

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Project description:IntroductionThe development of stress-related psychopathologies, often associated with socio-emotional dysfunctions, is crucially determined by genetic and environmental factors, which shape the individual vulnerability or resilience to stress. Especially early adolescence is considered a vulnerable time for the development of psychopathologies. Various mouse strains are known to age-dependently differ in social, emotional, and endocrine stress responses based on genetic and epigenetic differences. This highlights the importance of the qualified selection of an adequate strain and age for any biomedical research. Neuropeptides like oxytocin (OXT) can contribute to individual and strain-dependent differences in emotional and social behaviors.MethodsIn this study, we compared anxiety- and fear-related, as well as social behavior and pain perception between male adolescent and adult mice of two commonly used strains, C57BL/6N (BL6) and CD1.ResultsWe revealed BL6 mice as being more anxious, less social, and more susceptible toward non-social and social trauma, both in adolescence and adulthood. Furthermore, during development from adolescence toward adulthood, BL6 mice lack the reduction in fear- and anxiety-related behavior seen in adult CD1 mice and show even higher social fear-responses and perception of noxious stimuli during adulthood. Analysis of the OXT system, by means of receptor autoradiography and immunohistochemistry, showed strain- and age-specific differences in OXT receptor (OXTR) binding in relevant brain regions, but no differences in the number of hypothalamic OXT neurons. However, intracerebroventricular infusion of OXT did neither reduce the high level of anxiety-related nor of social fear-related behavior in adult BL6 mice.DiscussionIn summary, we show that male BL6 mice present an anxious and stress vulnerable phenotype in adolescence, which further exacerbates in adulthood, whereas CD1 mice show a more resilient socio-emotional state both in adolescence as well as during adulthood. These consistent behavioral differences between the two strains might only be partly mediated by differences in the OXT system but highlight the influence of early-life environment on socio-emotional behavior.

Project description:BackgroundAnimal models used to study pathologies requiring rehabilitation therapy, such as cardiovascular and neurologic disorders or oncologic disease, must be as refined and translationally relevant as possible. Sometimes, however, experimental procedures such as those involving restraint may generate undesired effects which may act as a source of bias. However, the extent to which potentially confounding effects derive from such routine procedures is currently unknown. Our study was therefore aimed at exploring possible undesirable effects of acute restraint stress, whereby animals were exposed to a brightly lit enclosed chamber (R&L) similar to those that are commonly used for substance injection. We hypothesised that this would induce a range of unwanted physiological alterations [such as neuroinflammatory response and changes in body weight and in brown adipose tissue (BAT)] and behavioural modification, and that these might be mitigated via the use of non-aversive handling methods: Tunnel Handling (NAH-T) and Mechanoceptive Handling (NAH-M)) as compared to standard Tail Handling (TH).MethodsTwo indicators of physiological alterations and three potentially stress sensitive behavioural parameters were assessed. Physiological alterations were recorded via body weight changes and assessing the temperature of Brown Adipose Tissue (BAT) using infra-red thermography (IRT), and at the end of the experiment we determined the concentration of cytokines CXCL12 and CCL2 in bone marrow (BM) and activated microglia in the brain. Nest complexity scoring, automated home-cage behaviour analysis (HCS) and Elevated Plus Maze testing (EPM) were used to detect any behavioural alterations. Recordings were made before and after a 15-minute period of R&L in groups of mice handled via TH, NAH-T or NAH-M.ResultsBAT temperature significantly decreased in all handling groups following R&L regardless of handling method. There was a difference, at the limit of significance (p = 0.06), in CXCL12 BM content among groups. CXCL12 content in BM of NAH-T animals was similar to that found in Sentinels, the less stressed group of animals. After R&L, mice undergoing NAH-T and NAH-M showed improved body-weight maintenance compared to those exposed to TH. Mice handled via NAH-M spent a significantly longer time on the open arms of the EPM. The HCS results showed that in all mice, regardless of handling method, R&L resulted in a significant reduction in walking and rearing, but not in total distance travelled. All mice also groomed more. No difference among the groups was found in Nest Score, in CCL2 BM content or in brain activated microglia.ConclusionsStress induced by a common restraint procedure caused metabolic and behavioural changes that might increase the risk of unexpected bias. In particular, the significant decrease in BAT temperature could affect the important metabolic pathways controlled by this tissue. R&L lowered the normal frequency of walking and rearing, increased grooming and probably carried a risk of low-grade neuro-inflammation. Some of the observed alterations can be mitigated by Non-aversive handlings.

Dataset Information

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

Publications

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

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