title: 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.
authors.affiliation: Osher Center for Integrative Medicine, University of California, San Francisco, California, United States of America. Blake.Gurfein@ucsf.edu
authors.forename: Blake T
authors.initials: BT
authors.lastname: Gurfein
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Stamm
authors.forename: Peter
authors.initials: P
authors.lastname: Bacchetti
authors.forename: Mary F
authors.initials: MF
authors.lastname: Dallman
authors.forename: Nachiket A
authors.initials: NA
authors.lastname: Nadkarni
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Milush
authors.forename: Chadi
authors.initials: C
authors.lastname: Touma
authors.forename: Rupert
authors.initials: R
authors.lastname: Palme
authors.forename: Charles Pozzo
authors.initials: CP
authors.lastname: Di Borgo
authors.forename: Gilles
authors.initials: G
authors.lastname: Fromentin
authors.forename: Rachel
authors.initials: R
authors.lastname: Lown-Hecht
authors.forename: Jan Pieter
authors.initials: JP
authors.lastname: Konsman
authors.forename: Michael
authors.initials: M
authors.lastname: Acree
authors.forename: Mary
authors.initials: M
authors.lastname: Premenko-Lanier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Darcel
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Nixon
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001823:Body Composition; D001835:Body Weight; D003345:Corticosterone / Q000096:biosynthesis; D004195:Disease Models, Animal; D002149:Energy Intake; D004777:Environment; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D036361:Peptide Hormones / Q000097:blood; D010805:Physical Conditioning, Animal; D013315:Stress, Psychological
chemical_list: D036361:Peptide Hormones; D003345:Corticosterone