Prolonged depression-like behavior caused by immune challenge: influence of mouse strain and social environment.
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ABSTRACT:
SUBMITTER: Painsipp E
PROVIDER: S-EPMC3108969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The emerging fungal pathogen, Batrachochytrium dendrobatidis (Bd), which can cause a fatal disease called chytridiomycosis, is implicated in the collapse of hundreds of host amphibian species. We describe chytridiomycosis dynamics in two co-occurring terrestrial salamander species, the Santa Lucia Mountains slender salamander, Batrachoseps luciae, and the arboreal salamander, Aneides lugubris. We (1) conduct a retrospective Bd-infection survey of specimens collected over the last century, (2) estimate present-day Bd infections in wild populations, (3) use generalized linear models (GLM) to identify biotic and abiotic correlates of infection risk, (4) investigate susceptibility of hosts exposed to Bd in laboratory trials, and (5) examine the ability of host skin bacteria to inhibit Bd in culture. Our historical survey of 2,866 specimens revealed that for most of the early 20th century (~1920-1969), Bd was not detected in either species. By the 1990s the proportion of infected specimens was 29 and 17% (B. luciae and A. lugubris, respectively), and in the 2010s it was 10 and 17%. This was similar to the number of infected samples from contemporary populations (2014-2015) at 10 and 18%. We found that both hosts experience signs of chytridiomycosis and suffered high Bd-caused mortality (88 and 71% for B. luciae and A. lugubris, respectively). Our GLM revealed that Bd-infection probability was positively correlated with intraspecific group size and proximity to heterospecifics but not to abiotic factors such as precipitation, minimum temperature, maximum temperature, mean temperature, and elevation, or to the size of the hosts. Finally, we found that both host species contain symbiotic skin-bacteria that inhibit growth of Bd in laboratory trials. Our results provide new evidence consistent with other studies showing a relatively recent Bd invasion of amphibian host populations in western North America and suggest that the spread of the pathogen may be enabled both through conspecific and heterospecific host interactions. Our results suggest that wildlife disease studies should assess host-pathogen dynamics that consider the interactions and effects of multiple hosts, as well as the historical context of pathogen invasion, establishment, and epizootic to enzootic transitions to better understand and predict disease dynamics.
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Project description:Mouse lines with behavioral phenotypes relevant to symptoms in neurodevelopmental disorders may provide models to test hypotheses about disease etiology and to evaluate potential treatments. The present studies were designed to confirm and expand earlier work on the intriguing behavioral profile of the C58/J inbred strain, including low social approach and aberrant repetitive movements. Additional tests were selected to reflect aspects of autism, a severe neurodevelopmental disorder characterized by emergence of symptoms early in life, higher prevalence in males, social deficits and abnormal repetitive behavior. Mice from the C57BL/6J inbred strain, which has a similar genetic lineage and physical appearance to C58/J, served as a comparison group. Our results revealed that C58/J mice display elevated activity levels by postnatal day 6, which persist into adulthood. Despite normal olfactory ability, young adult male C58/J mice showed deficits in social approach in the three-chambered choice assay and failed to demonstrate social transmission of food preference. In contrast, female C58/J mice performed similarly to female C57BL/6J mice in both social tests. C58/J mice of both sexes demonstrated abnormal repetitive behaviors, displaying excessive jumping and back flipping in both social and non-social situations. These stereotypies were clearly evident in C58/J pups by postnatal days 20-21, and were also observed in C58/J dams during a test for maternal behavior. Overall, the strain profile for C58/J, including spontaneously developing motor stereotypies emerging early in the developmental trajectory, and social deficits primarily in males, models multiple components of the autism phenotype.
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Project description:The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation to tissue responses to HU. To accomplish this, we developed a refinement to the traditional NASA Ames single housing HU system to accommodate social housing in pairs, retaining desirable features of the original design. We conducted a 30-day HU experiment with adult, female mice that were either singly or socially housed. HU animals in both single and social housing displayed expected musculoskeletal deficits versus housing matched, normally loaded (NL) controls. However, select immune and hypothalamic-pituitary-adrenal (HPA) axis responses were differentially impacted by the HU social environment relative to matched NL controls. HU led to a reduction in % CD4+ T cells in singly housed, but not in socially housed mice. Unexpectedly, HU increased adrenal gland mass in socially housed but not singly housed mice, while social isolation increased adrenal gland mass in NL controls. HU also led to elevated plasma corticosterone levels at day 30 in both singly and socially housed mice. Thus, musculoskeletal responses to simulated weightlessness are similar regardless of social environment with a few differences in adrenal and immune responses. Our findings show that combined stressors can mask, not only exacerbate, select responses to HU. These findings further expand the utility of the HU model for studying possible combined effects of spaceflight stressors.
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Project description:BackgroundThe fields of environment and health are both interdisciplinary and trans-disciplinary, and until recently had little engagement in social networking designed to cross disciplinary boundaries. The EU FP6 project HENVINET aimed to establish integrated social network and networking facilities for multiple stakeholders in environment and health. The underlying assumption is that increased social networking across disciplines and sectors will enhance the quality of both problem knowledge and problem solving, by facilitating interactions. Inter- and trans-disciplinary networks are considered useful for this purpose. This does not mean that such networks are easily organized, as openness to such cooperation and exchange is often difficult to ascertain.MethodsDifferent methods may enhance network building. Using a mixed method approach, a diversity of actions were used in order to investigate the main research question: which kind of social networking activities and structures can best support the objective of enhanced inter- and trans-disciplinary cooperation and exchange in the fields of environment and health. HENVINET applied interviews, a role playing session, a personal response system, a stakeholder workshop and a social networking portal as part of the process of building an interdisciplinary and trans-disciplinary network.ResultsThe interviews provided support for the specification of requirements for an interdisciplinary and trans-disciplinary network. The role playing session, the personal response system and the stakeholder workshop were assessed as useful tools in forming such network, by increasing the awareness by different disciplines of other's positions. The social networking portal was particularly useful in delivering knowledge, but the role of the scientist in social networking is not yet clear.ConclusionsThe main challenge in the field of environment and health is not so much a lack of scientific problem knowledge, but rather the ability to effectively communicate, share and use available knowledge for policy making. Structured social network facilities can be useful by policy makers to engage with the research community. It is beneficial for scientists to be able to integrate the perspective of policy makers in the research agenda, and to assist in co-production of policy-relevant information. A diversity of methods need to be applied for network building: according to the fit-for-purpose-principle. It is useful to know which combination of methods and in which time frame produces the best results.Networking projects such as HENVINET are created not only for the benefit of the network itself, but also because the applying of the different methods is a learning tool for future network building. Finally, it is clear that the importance of specialized professionals in enabling effective communication between different groups should not be underestimated.
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Project description:Background The environment plays a large role in the health of individuals; however, more research is needed to better understand aspects of the environment that most influence health. Specifically, our study examines how the social environment influences cardiovascular health (CVH). Methods and Results The social environment was characterized using measures of belonging and life and work stress in individuals, as well as nationally derived measures of marginalization, deprivation, economic status, and community well-being in neighborhoods. CVH was defined by the American Heart Association's Cardiovascular Health Index-a summed score of 7 clinical and behavioral components known to have the greatest impact on CVH. Data were obtained from the Canadian Community Health Survey 2015 to 2016 and multiple national data sources. Multilevel regression models were used to analyze the associations between CVH and the social environment. Overall, 27% of Canadians reported ideal CVH (6-7 score points), 68% reported intermediate CVH (3-5 score points), and 5% reported poor CVH (0-2 score points). The neighborhood environment contributed up to 7% of the differences in CVH between individuals. Findings indicated that residing in a neighborhood with greater community well-being (odds ratio [OR], 1.33 [95% CI, 1.26-1.41]) was associated with achieving higher odds of ideal CVH, while weaker community belonging (OR, 0.67 [95% CI, 0.62-0.72]) and residing in a neighborhood with greater marginalization (OR, 0.87 [95% CI, 0.82-0.91]) and deprivation (OR, 0.67 [95% CI, 0.64-0.69]) were associated with achieving lower odds of ideal CVH. Conclusions Aspects of individual-level social environment and residing in a neighborhood with a more favorable social environment were both independently and significantly associated with achieving ideal CVH.
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Project description:Social dominance encompasses winning dyadic contests and gaining priority access to resources and reproduction. Disposition to dominance is influenced by environmental factors, particularly during early postnatal life and adolescence. A disinhibitory mPFC microcircuit has been implicated in the expression of dominance in the “tube test” paradigm of social competition in mice, but the neuronal and transcriptional plasticity associated with the environment induced increase in social dominance is not known. We previously reported that male pups raised by physically active (as opposed to sedentary) dams exhibit dominance and increased reproductive fitness, and here we show that social isolation from weaning also increases dominance. By using these preweaning and postweaning environmental models, we tested if dominance is associated with transcriptional plasticity and a specific transcriptional profile in one or more cell types in the mPFC. Given that the mPFC is composed of several cell types, we used single cell transcriptomics to characterize the influence of the preweaning maternal and postweaning social environment on cell-type specific gene expression. The preweaning maternal effect, but not postweaning social isolation, caused gene expression changes in a wide range of cell types including pyramidal neurons, various interneurons, and astrocytes. However, both the maternal effect and social isolation induced the coordinated downregulation of synaptic channel, receptor, and adhesion genes in parvalbumin positive (PV) interneurons. This suggests an impaired PV interneuron-mediated inhibition of pyramidal cells in animals predisposed to dominance, a notion consistent with dominant behavior being driven by the disinhibition of mPFC pyramidal neurons.
2024-01-31 | GSE234726 | GEO
Project description:Early life stress (ELS), such as neglect and maltreatment, exhibits a strong impact on the mental and brain development of children. However, it is not fully understood how ELS affects the function in developing prefrontal cortex (PFC). In this study, we performed social isolation on weaned pre-adolescent mice and investigated how ELS could affect the function in behavior and transcriptome in PFC. We found that reductions of social interaction, social preference, and social novelty in ELS mice. Moreover, an increase of anxiety-like behavior was observed in ELS mice, but there were no changes in weight and repetitive behavior. To identify the gene involved in social behavior, we conducted transcriptome analysis and identified 15 differentially expressed genes (DEGs) in the PFC of ELS mice. These genes were involved in transcriptional regulation, stress, and synaptic signaling. We also found that a decreased number of neurons and an increased number of microglia in the PFC of ELS mice. These results suggest that ELS affects PFC cytoarchitecture by stress signal transduction and eventually alters mouse behavior. Our study demonstrates that ELS influences behavior, transcriptome and cytoarchitecture in the brain of adolescent mice.
2021-11-30 | GSE180055 | GEO