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Environmental Enrichment and Rat Liver Proteomics

ABSTRACT: We aimed to address the challenge of accommodating an increasing demand for aged laboratory animals in the context of rising elderly population and research on aging-related diseases. We developed a cost-effective environmental enrichment method and assessed its impact on metabolic changes in Sprague Dawley rats' livers as a proof-of-concept organ. Twenty-four male rats were divided into four groups, with two kept in standard cages and two in modified rabbit cages. Half of each type of cage group received additional enrichment through weekly playtime in a larger cage. Over six months, the rats' weight gain was consistent across all groups, and corticosterone levels did not significantly differ. However, the control group had significantly lower DHEA and Testosterone levels at the study's end. Rats in enriched environments exhibited less distress during inspections and were more resistant to accepting treats. Animals accustomed to playpen time left their cages more easily. Overall, the study demonstrated that refining husbandry for aging rats is both simple and cost-effective, without detrimental effects on stress levels, development, or liver metabolism.

INSTRUMENT(S): impact II

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Liver

SUBMITTER: Simon Moosburner

LAB HEAD: Prof. Dr. Igor M. Sauer

PROVIDER: PXD046110 | Pride | 2024-01-22

REPOSITORIES: Pride

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Project description:Pneumocystis is a pathogen of immunocompromised hosts but can also infect healthy hosts, in whom infection is rapidly controlled and cleared. To better understand the immune mechanisms contributing to clearance of infection, microarray methods were used to examine differential gene expression in the lungs of C57BL/6 and CD40 ligand knock-out (CD40L-KO) mice over time following exposure to Pneumocystis. Immuncompetent C57BL/6 mice, which control and clear infection efficiently, showed a robust response to infection characterized by the upregulation of 349 primarily immune-response associated genes. Temporal changes in the expression of these genes suggested that there was an early (week 2) primarily innate response, that waned without controlling infection; this were followed by primarily adaptive immune responses that peaked at week 5 and successfully cleared the infection. In conjunction with the latter, there was an increased expression of B cell associated (immunoglobulin) genes at week 6 that persisted through 11 weeks. In contrast, CD40L-KO mice, which are highly susceptible to developing severe Pneumocystis pneumonia, showed essentially no upregulation of immune-response associated genes at days 35 to 75. Immunohistochemical staining supported these observations by demonstrating an increase in CD4+, CD68+, and CD19+ cells in C57BL/6 but not CD40L-KO mice. Thus, the healthy host demonstrates a robust biphasic response to infection by Pneumocystis; CD40 ligand is an essential upstream regulator of the adaptive immune responses that efficiently control infection and prevent development of progressive pneumonia. Keywords: Time course response Pneumocystis murina infection wild type versus CD40L-KO mice In experiment 1, C57BL/6 and CD40L-KO mice were co-housed in 2 cages; one cage was exposed to a P. murina-infected seeder, while the second was unexposed. Mice (3 per group) were sacrificed at day 32. Because the initial study demonstrated very little change in gene expression in CD40L-KO mice, only C57BL/6 mice were used for experiments 2 and 3. In Experiment 2, three cages (10 animals/cage) were set up: 2 cages were exposed to P. murina, and one was unexposed. Animals (5 per cage) were sacrificed at days 34 and 41. In Experiment 3, which focused on gene expression early after exposure to P. murina, five cages (9-10 animals/cage) were set up, of which 3 were exposed and 2 were unexposed. Animals (1-3 per cage) were sacrificed at days 7, 14 and 21 of exposure. Experiment 4 was designed to verify the initial results in CD40L-KO mice, and included 5 unexposed controls and 4 mice exposed for 35 days.

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Environmental Enrichment and Rat Liver Proteomics

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