The immunomodulatory effects of social isolation in mice are linked to temperature control

Hamilton, Alice; Rizzo, Raffaella; Brod, Samuel; Ono, M.; Perretti, Mauro; Cooper, Dianne; D’Acquisto, Fulvio

doi:10.1016/j.bbi.2022.02.022

Cited by 8 publications

(6 citation statements)

References 153 publications

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“…No changes in monocytes and granulocytes were observed in single-housed animals after 7 days, although changes were found after 4 weeks. A previous study found no significant differences in the overall number of blood-circulating leukocytes between CD1 male mice that were socially isolated for 2 weeks and their socially housed counterparts [ 36 ]. However, C57BL6/J adult mice separated into individual cages for 2 h every day for 25 days were found to have a decrease in T cells, B cells, monocytes, and neutrophils [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…The effect of solitary versus social housing on corticosterone levels has been explored with varying results. Some studies observed that single-housed male mice had increased corticosterone levels after 14 days [ 30 ] and 15 months [ 31 ], whereas others found that corticosterone levels remained stable up to 42 days of individual housing [ 32 , 33 , 34 , 35 , 36 ], and two studies reported that single housing caused less stress for mice than group housing [ 37 , 38 ]. Other indications of stress include changes in body weight and a decrease in circulating leukocytes.…”

Section: Introductionmentioning

confidence: 99%

“…A meta-analysis of the effects of individual housing on body weight found considerable heterogeneity in different mice strains, with higher, unchanged, or lower body weights being reported after social isolation [ 39 ]. Although it is well documented that chronic stress results in immunosuppression [ 40 ], differences in the total number of white blood cells have also been observed [ 36 , 41 ]. Among other factors, these discrepancies may be due to differing isolation periods.…”

Section: Introductionmentioning

confidence: 99%

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Individualized Housing Modifies the Immune–Endocrine System in CD1 Adult Male Mice

Ortega-Saez

Díez-Solinska

Grífols

et al. 2023

Animals

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In the last years, different research groups have made considerable efforts to improve the care and use of animals in research. Mice (Mus musculus) are the most widely used animal species in research in the European Union and are sociable and hierarchical creatures. During experiments, researchers tend to individualize males, but no consideration is given to whether this social isolation causes them stress. The aim of this study was, therefore, to explore whether 4 weeks of social isolation could induce changes in different physiological parameters in adult Crl:CD1(ICR) (CD1) males, which may interfere with experimental results. Body weight, blood cells, and fecal corticosterone metabolites levels were the analyzed parameters. Blood and fecal samples were collected at weeks 1 and 4 of the experimental procedure. Four weeks of single housing produced a significant time-dependent decrease in monocytes and granulocytes. Fecal corticosterone metabolite levels were higher in single-housed mice after 1 week and then normalized after 4 weeks of isolation. Body weight, red blood cells, and platelets remained unchanged in both groups during this period. We can, therefore, conclude that social isolation affects some immune and endocrine parameters, and that this should be taken into account in the interpretation of research data.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Individualized Housing Modifies the Immune–Endocrine System in CD1 Adult Male Mice

Ortega-Saez

Díez-Solinska

Grífols

et al. 2023

Animals

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“…If catecholamines are increased in response to social isolation, this could reduce bone mass via beta-2 adrenergic (β2AR) signaling [40] , [41] . Another possibility is that social isolation at room temperature (versus thermoneutral) leads to thermal stress in mice and consequently heightened SNS activity [42] , [43] to stimulate brown adipose thermogenesis. This could then lead to bone loss due to cold stress [44] , [45] , [46] , [47] .…”

Section: Discussionmentioning

confidence: 99%

Social isolation through single housing negatively affects trabecular and cortical bone in adult male, but not female, C57BL/6J mice

Mountain

Langlais

et al. 2023

Bone

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“…If catecholamines are increased in response to social isolation, this could reduce bone mass via beta-2 adrenergic (β2AR) signaling 39,40 . Another possibility is that social isolation at room temperature (versus thermoneutral) leads to thermal stress in mice and consequently heightened SNS activity 41,42 to stimulate brown adipose thermogenesis. This could then lead to bone loss due to cold stress [43][44][45][46] .…”

Section: Discussionmentioning

confidence: 99%

Social Isolation Causes Cortical and Trabecular Bone Loss in Adult Male, but not Female, C57BL/6J Mice

Mountain¹,

Langlais

et al. 2023

Preprint

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Social isolation is a potent form of psychosocial stress and is a growing public health concern, particularly among older adults. Even prior to the onset of the COVID-19 pandemic, which has significantly increased the prevalence of isolation and loneliness, researchers have been concerned about a rising "epidemic" of loneliness. Isolation is associated with an increased risk for many physical and mental health disorders and increased overall mortality risk. In addition to social isolation, older adults are also at greater risk for osteoporosis and related fractures. While researchers have investigated the negative effects of other forms of psychosocial stress on bone, including depression and PTSD, the effects of social isolation on bone have not been thoroughly investigated. The aim of this study was to test the hypothesis that social isolation would lead to bone loss in male and female C57BL/6J mice. 16-week-old mice were randomized into social isolation (1 mouse/cage) or grouped housing (4 mice/cage) for four weeks (N=16/group). Social isolation significantly decreased trabecular (BV/TV, BMD, Tb. N., Tb. Th.) and cortical bone (Ct.Th., Ct.Ar., Ct.Ar./Tt.Ar., pMOI, Ct.Por.) parameters in male, but not female mice. Isolated male mice had signs of reduced bone remodeling represented by reduced osteoblast numbers, osteoblast-related gene expression and osteoclast-related gene expression. However, isolated females had increased bone resorption-related gene expression, without any change in bone mass. Overall, our data suggest that social isolation has negative effects on bone in males, but not females, although females showed suggestive effects on bone resorption. These results provide critical insight into the effects of isolation on bone and have key clinical implications as we grapple with the long-term health impacts of the rise in social isolation related to the COVID-19 pandemic.

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The immunomodulatory effects of social isolation in mice are linked to temperature control

Cited by 8 publications

References 153 publications

Individualized Housing Modifies the Immune–Endocrine System in CD1 Adult Male Mice

Individualized Housing Modifies the Immune–Endocrine System in CD1 Adult Male Mice

Social isolation through single housing negatively affects trabecular and cortical bone in adult male, but not female, C57BL/6J mice

Social Isolation Causes Cortical and Trabecular Bone Loss in Adult Male, but not Female, C57BL/6J Mice

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