Thermoneutral Housing has Limited Effects on Social Isolation-Induced Bone Loss in Male C57BL/6J Mice

Abstract

Social isolation stress has numerous known negative health effects, including increased risk for cardiovascular disease, dementia, as well as overall mortality. The impacts of social isolation on skeletal health, however, have not been thoroughly investigated. We previously found that four weeks of social isolation through single housing led to a significant reduction in trabecular and cortical bone in male, but not female, mice. One possible explanation for these changes in male mice is thermal stress due to sub-thermoneutral housing. Single housing at room temperature (~20-25 deg C) - below the thermoneutral range of mice (~26-34 deg C) - may lead to cold stress, which has known negative effects on bone. Therefore, the aim of this study was to test the hypothesis that housing mice near thermoneutrality, thereby ameliorating cold-stress, will prevent social isolation-induced bone loss in male C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) at either room temperature (~23 deg C) or in a warm temperature incubator (~28 deg C) for four weeks (N=8/group). As seen in our previous studies, isolated mice at room temperature had significantly reduced bone parameters, including femoral bone volume fraction (BV/TV), bone mineral density (BMD), and cortical thickness. Contrary to our hypothesis, these negative effects on bone were not ameliorated by thermoneutral housing. Social isolation increased glucocorticoid-related gene expression in bone and Ucp1 and Pdk4 expression in BAT across temperatures, while thermoneutral housing increased percent lipid area and decreased Ucp1 and Pdk4 expression in BAT across housing conditions. Overall, our data suggest social isolation-induced bone loss is not a result of thermal stress from single housing and provides a key insight into the mechanism mediating the effects of isolation on skeletal health.