| Summary: | Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, suppressed immunity, and central nervous system neuropathology. While human studies have illustrated the benefits of stress reduction, mechanistic understanding of how decreasing stress affects health, and disease progression remains unclear. Furthermore, prior animal studies have focused primarily on increasing stress, and few animal models of stress reduction have been fully developed. Therefore, we have developed a “calm mouse model” with caging enhancements designed to reduce murine stress.Male BALB/c mice were divided into four groups (n=10/group): Control (Cntl), standard caging; Calm (Calm), large caging to reduce animal density, a cardboard nest box for shelter, paper nesting material to promote innate nesting behavior, and a polycarbonate tube to mimic tunneling; Control Exercise (Cntl Ex), standard caging with a running wheel, known to reduce stress; Calm Exercise (Calm Ex), Calm caging with a running wheel.Calm, Cntl Ex, and Calm Ex animals exhibited significantly less corticosterone production than Cntl (Day 49: Calm, Mdiff 20.5 ng corticosterone metabolites/0.05 g feces (CM), CI95 11.7–29.4, P<0.0001; Cntl Ex, Mdiff 22.5 ng CM, CI95 13.4–31.5, P<0.0001; Calm Ex, Mdiff 21.8 CM, CI95 11.7–32.0, P=0.0003). Calm animals gained greater body mass than Cntl, although they had similar weekly energy intake. We also observed changes in body composition, spleen mass, and spleen composition. In particular, we found that Calm mice had a significantly greater proportion and absolute number of splenic CD19+ B lymphocytes when compared with Cntl (proportion: Mdiff 6.7% of splenocytes, P<0.0001; absolute number: Mdiff 9.04 × 106 cells, CI95 8.3×106–9.8×106, P<0.0001).Our data indicate that both Calm and exercise caging generated reductions in physiologic stress measures in mice and that Calm animals exhibited increases in splenocyte subpopulations that may underlie changes in functional immunity. Collectively, the Calm model represents a promising approach to studying the biological effects of stress reduction in the context of health and in conjunction with disease models.
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