The Calm Mouse: An Animal Model of Stress Reduction

Abstract

Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, deleterious effects on innate and adaptive immunity, and central nervous system neuropathology. Although stress management is commonly advocated clinically, there is insufficient mechanistic understanding of how decreasing stress affects disease pathogenesis. 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: 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; and calm exercise (Calm Ex), calm caging with a running wheel. Calm, Cntl Ex and Calm Ex animals exhibited significantly less corticosterone production than Cntl animals. We also observed changes in spleen mass, and in vitro splenocyte studies demonstrated that Calm Ex animals had innate and adaptive immune responses that were more sensitive to acute handling stress than those in Cntl. Calm animals gained greater body mass than Cntl, although they had similar food intake, and we also observed changes in body composition, using magnetic resonance imaging. Together, our results suggest that the Calm mouse model represents a promising approach to studying the biological effects of stress reduction in the context of health and in conjunction with existing disease models.

Enriched environment and stress exposure influence splenic B lymphocyte composition

“…Previously [23], we have shown that caging environments that mimic elements of a natural murine habitat such as providing access to an exercise wheel can substantially influence various aspects of mouse physiology. To increase the degree to which animal studies successfully translate, it may be worth investigating whether standard housing conditions appear to be artificial and more suited for convenience, rather that reproducing more natural housing conditions.…”

Regulation of nonsmall‐cell lung cancer stem cell like cells by neurotransmitters and opioid peptides

“…Control mice were housed under standard conditions recommended by IACUC for the maintenance of mice: 4 animals per cage in polycarbonate cages (189 3 297 3 128 mm 3 ) provided with standard corn cob bedding, autoclaved tap water and irradiated food ad libitum. In accord with published procedures, 29 stress reduction was achieved in the treatment group by housing the same number of mice in larger polycarbonate cages (257 3 483 3 152 mm 3 ) provided with the following enrichment items: two polycarbonate tunnels (Bio-Serv) to allow tunneling behavior, two paper nest boxes (Bio-Serv) and nesting material (compressed Envirodry Eco-bedding paper strips, Fibercore) for shelter and enhancement of nesting behavior. All enrichment items were autoclaved prior to use.…”

“…Using in vitro studies with cancer stem cell like cells (CSCs) enriched by spheroid formation assays from three NSCLC cell lines in conjunction with environmental and enrichment strategies reported to generate the “calm mouse”, an animal model for stress reduction and well‐being, in athymic mice carrying NSCLC xenografts, our current data provide evidence, for the first time, that stress neurotransmitters significantly increase the number of CSCs via cAMP‐driven stimulation of the SHH pathway and ALDH‐1 and that these responses are inhibited by pharmacologically or psychologically‐induced increases in GABA or opioid peptides.…”

Environmental enrichment alleviates the deleterious effects of stress in experimental autoimmune encephalomyelitis

“…Environmental enrichment has been described as an efficient paradigm to reduce stress in laboratory rodents 9 . Here, we bred mice in standard or enriched environment prior to EAE induction and exposure to repeated acute stress ( Figure 3A-B).…”