Dataset Information

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

ACCESS DATA

Similar Datasets

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.

Project description:Sustained caloric restriction (CR) extends lifespan in animal models but the mechanism and primary tissue target(s) have not been identified. Gene expression changes with aging and CR were examined in both heart and subcutaneous white adipose tissue (WAT) of F344 male rats using AffymetrixÂ® RAE 230 arrays and validated by qRT-PCR on 18 genes. In heart, age- associated changes but not CR-associated changes in old. In WAT, genes were identified where the aging change is suppressed by CR (candidate markers of healthy aging) and those affected by CR but not normal aging (candidate longevity assurance genes). 10-21% of age-associated genes were regulated in common between tissues. Gene set enrichment analysis (GSEA) revealed coordinate small magnitude changes in ribosomal, proteasomal, and mitochondrial genes with similarities between heart and WAT. Further analysis revealed PPARgamma as a potential upstream regulator of altered gene expression in old CR WAT. These results demonstrate a reduced mRNA response to CR with age in heart relative to WAT. In WAT, we identified candidate CR mimetic targets and candidate markers of healthy aging. These data suggest a role for subcutaneous WAT in the effects of CR and strengthen the role for PPAR signaling in aging and CR while indicating that the effects of CR in heart can occur independent of global changes in mRNA level. Experiment Overall Design: Tissues (n=5-7 animals per group) were obtained from the NIH-NIA aging rodent tissue bank. According to supplier records, animals were housed in a specific pathogen free barrier facility under contract with BioReliance. AL animals were housed 3 per cage and CR animals were housed singly. CR (60% of AL) was initiated at 4 months of age with a switch from the NIH 31 to NIH fortified diet. F344 male rats were sacrificed at 4 months (4AL) or 28 months of age (28AL, 28CR). Animals with gross tumor pathologies were excluded from the study. All animals were euthanized by CO2 asphixiation and tissues were frozen in liquid nitrogen then stored at â80Â°C. Subcutaneous WAT was collected from the abdominal region. Recorded body weights differed dramatically between the 3 groups (4AL = 253Â±8 g, 28AL = 382Â±20 g, 28CR = 288Â±7 g) and heart weight as a fraction of body weight was not significantly different between the groups (data not shown). The apical ~1/3 of the heart was homogenized for the expression studies. Sections from the cut face were stained with haematoxylin and eosin to confirm expected aging-associated pathology changes.

Dataset Information

Environmental Enrichment and Rat Liver Proteomics

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure